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| 4. |
- Ahlenius, Sven, et al.
(author)
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Prolongation of the ejaculation latency in the male rat by thioridazine and chlorimipramine.
- 1979
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In: Psychopharmacology. - 0033-3158 .- 1432-2072. ; 65:2, s. 137-140
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Journal article (peer-reviewed)abstract
- Thioridazine (3 mg/kg) and chlorimipramine (1.5–6.0 mg/kg) prolonged the ejaculation latency and increased the number of mounts but did not change the number of intromissions preceding ejaculation. Blockade of peripheral and central noradrenaline receptors by phentolamine and phenoxybenzamine respectively resulted in a suppression of all aspects of the sexual behavior with increasing doses. dl-5-HTP (25–100 mg/kg) in combination with an inhibitor of peripheral 5-HTP decarboxylase (benserazide, 25 mg/kg) produced, like chlorimipramine and thioridazine, a prolongation of ejaculation latency and an increase in the number of mounts preceding ejaculation. Selective inhibition of 5-HT reuptake however, by zimelidine (0–20 mg/kg) or alaproclate (0–20 mg/kg) did not affect the mating behavior. At higher doses of these drugs some animals failed to initiate sexual activities. There was an increase in the postejaculatory interval but no change in the ejaculatory latency.It is concluded that the prolonged ejaculation latencies observed following treatment with thioridazine or chlorimipramine is not due to a blockade of central or peripheral adrenergic -receptors.
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| 5. |
- Allard, Per, et al.
(author)
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Unaltered [3H]GBR-12935 binding after chronic treatment with dopamine active drugs.
- 1990
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In: Psychopharmacology. - 0033-3158 .- 1432-2072. ; 102:3, s. 291-4
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Journal article (peer-reviewed)abstract
- Rats were injected intraperitoneally with haloperidol 0.5 mg/kg, raclopride 1 mg/kg, bromocriptine 2.5 mg/kg, d-amphetamine 2.5 mg/kg, or cocaine 10 mg/kg twice daily for 21 days. The animals were sacrificed 72 h after last injection. Control rats were injected with saline, following the same schedule. The radioligand [3H]GBR-12935 was used as a presynaptic marker for dopamine neurites. There were no significant differences in [3H]GBR-12935 binding to striatum between drug-treated rats and controls.
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| 6. |
- Alsiö, Johan, et al.
(author)
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The role of 5-HT2C receptors in touchscreen visual reversal learning in the rat : a cross-site study
- 2015
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In: Psychopharmacology. - : Springer Science and Business Media LLC. - 0033-3158 .- 1432-2072. ; 232:21-22, s. 4017-4031
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Journal article (peer-reviewed)abstract
- Reversal learning requires associative learning and executive functioning to suppress non-adaptive responding. Reversal-learning deficits are observed in e.g. schizophrenia and obsessive-compulsive disorder and implicate neural circuitry including the orbitofrontal cortex (OFC). Serotonergic function has been strongly linked to visual reversal learning in humans and experimental animals but less is known about which receptor subtypes are involved. The objectives of the study were to test the effects of systemic and intra-OFC 5-HT2C-receptor antagonism on visual reversal learning in rats and assess the psychological mechanisms underlying these effects within novel touchscreen paradigms. In experiments 1-2, we used a novel 3-stimulus task to investigate the effects of 5-HT2C-receptor antagonism through SB 242084 (0.1, 0.5 and 1.0 mg/kg i.p.) cross-site. Experiment 3 assessed the effects of SB 242084 in 2-choice reversal learning. In experiment 4, we validated a novel touchscreen serial visual reversal task suitable for neuropharmacological microinfusions by baclofen-/muscimol-induced OFC inactivation. In experiment 5, we tested the effect of intra-OFC SB 242084 (1.0 or 3.0 mu g/side) on performance in this task. In experiments 1-3, SB 242084 reduced early errors but increased late errors to criterion. In experiment 5, intra-OFC SB 242084 reduced early errors without increasing late errors in a reversal paradigm validated as OFC dependent (experiment 4). Intra-OFC 5-HT2C-receptor antagonism decreases perseveration in novel touchscreen reversal-learning paradigms for the rat. Systemic 5-HT2C-receptor antagonism additionally impairs late learning-a robust effect observed cross-site and potentially linked to impulsivity. These conclusions are discussed in terms of neural mechanisms underlying reversal learning and their relevance to psychiatric disorders.
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| 7. |
- Andersson, Jan, et al.
(author)
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Oxygen saturation and cognitive performance.
- 2002
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In: Psychopharmacology. - : Springer Science and Business Media LLC. - 0033-3158 .- 1432-2072. ; 162:2, s. 119-128
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Journal article (peer-reviewed)abstract
- The purpose of the experiments was to investigate how inhalation of 100% oxygen affected cognitive performance. A test battery was developed that was designed to capture different aspects of cognitive processes, i.e., perception, attention, working memory, long-term memory and prospective memory. All tests were verbally based, thus reducing cognitive spatial processes to a minimum. In experiment 1, 48 participants volunteered in a complete factorial within-participant design. Two different conditions for type of gas were used, inhalation of 100% oxygen and inhalation of breathing air (approximately 21% oxygen balanced with nitrogen). The inhalation was performed during the 1 min prior to starting each separate test. The instructions for each test were given during the inhalation period. All participants inhaled oxygen or breathing air through a Swedish military pilot mask. Physiological (heartbeats per minute and blood oxygen saturation level) reactions were recorded continuously throughout the session. Participants also completed a mood-state questionnaire before and after the test battery. The results revealed that cognitive performance were not affected by inhalation. Hence, this experiment does not replicate previous findings that suggest that inhalation of 100% oxygen could increase cognitive performance. Another experiment was performed to control for methodological issues. Experiment 2 revealed exactly the same pattern, i.e., inhalation of oxygen did not affect cognitive functioning.
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| 14. |
- Atkins, Alison Lynn, 1976-, et al.
(author)
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Stereotypic behaviors in mice selectively bred for high and low methamphetamine-induced stereotypic chewing.
- 2001
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In: Psychopharmacology. - Heidelberg : Springer Science and Business Media LLC. - 0033-3158 .- 1432-2072. ; 157:1, s. 96-104
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Journal article (peer-reviewed)abstract
- RATIONALE: At high doses, methamphetamine produces repetitive stereotypic behaviors, and the degree to which this occurs is heritable.OBJECTIVES: Mice of a B6D2F2 genetic background were selectively bred for four generations for high (HMA) and low (LMA) numbers of stereotyped chewing episodes measured for 1 min at 33 min post-injection following 10 mg/kg methamphetamine (changed to 7 mg/kg for the high line and 15 mg/kg for the low line in the third selected generation to avoid ceiling and floor effects, respectively). We sought to determine whether stereotypic behaviors other than number of repetitive chewing episodes were altered by the selective breeding process.METHODS: HMA and LMA mice of the third and fourth selected generations were tested for chewing stereotypy, for a number of other stereotypic behaviors previously observed in rodents, and for several other non-stereotypic responses to methamphetamine. Testing in the third selected generation was conducted by observing behaviors on videotape following 7 mg/kg methamphetamine. In the fourth selected generation, mice were also tested in automated activity monitors following 10 mg/kg methamphetamine and in climbing chimneys following 16 mg/kg methamphetamine. Dose-response curves with doses of 1, 2, 3.5, 7, 10, and 15 mg/kg methamphetamine were constructed for the most commonly observed behaviors.RESULTS: LMA mice, which exhibited low stereotyped chewing, exhibited high stereotyped circling and climbing, and the reverse was true for these behaviors for HMA mice. For most of the other behaviors measured, there were drug effects but no differences between selected lines.CONCLUSIONS: These results suggest that these three stereotyped behaviors, chewing, circling, and climbing, at least partly share the same mechanisms, and therefore are influenced by at least some of the same genes, since animals selectively bred for low methamphetamine-induced stereotyped chewing exhibited high amounts of circling and climbing when given methamphetamine. This also suggests that the other stereotypic behaviors that we measured do not occur by the same genetically determined mechanisms as stereotypic chewing.
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| 15. |
- Azadi, Maryam, et al.
(author)
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Preconception paternal morphine exposure leads to an impulsive phenotype in male rat progeny
- 2021
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In: Psychopharmacology. - : Springer Nature. - 0033-3158 .- 1432-2072. ; 238, s. 3435-3446
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Journal article (peer-reviewed)abstract
- Rationale Identifying the long-term neurocognitive implications of opioid addiction may further our understanding of the compulsive nature of this brain disorder. The aim of this study was to examine the effects of paternal adolescent opiate exposure on cognitive performance (visual attention, impulsivity, and compulsivity) in the next generation. Methods Male Wistar rats received escalating doses of morphine (2.5-25 mg/kg, s.c.) or saline for 10 days during adolescence (P30-39). In adulthood (P70-80), these rats were allowed to mate with drug-naive females. Male offspring from morphine- and saline-exposed sires, once in adulthood, were trained and tested in the 5-choice serial reaction time test (5-CSRTT) to evaluate their cognitive abilities under baseline, drug-free conditions as well as following acute (1, 3, 5 mg/kg morphine) and subchronic morphine (5 mg/kg morphine for 5 days) treatment. Behavioral effects of the opioid receptor antagonist naloxone were also assessed. Results Morphine-sired offspring exhibited delayed learning when the shortest stimulus duration (1 s) was introduced, i.e., when cognitive load was highest. These subjects also exhibited a reduced ability to exert inhibitory control, as reflected by increased premature and perseverative responding under drug-free baseline conditions in comparison to saline-sired rats. These impairments could not be reversed by administration of naloxone. Moreover, impulsive behavior was further enhanced in morphine-sired rats following acute and subchronic morphine treatment. Conclusion Paternal opiate exposure during adolescence was found to primarily impair inhibitory control in male progeny. These results further our understanding of the long-term costs and risk of opioid abuse, extending across generations.
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| 16. |
- Aziz, Abdul Maruf Asif, et al.
(author)
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The nociceptin/orphanin FQ receptor agonist SR-8993 as a candidate therapeutic for alcohol use disorders: validation in rat models
- 2016
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In: Psychopharmacology. - : Springer. - 0033-3158 .- 1432-2072. ; 233:19-20, s. 3553-3563
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Journal article (peer-reviewed)abstract
- RATIONALE: Alcoholism is a complex disorder in which diverse pathophysiological processes contribute to initiation and progression, resulting in a high degree of heterogeneity among patients. Few pharmacotherapies are presently available, and patient responses to these are variable. The nociceptin/orphanin FQ (NOP) receptor has been suggested to play a role both in alcohol reward and in negatively reinforced alcohol seeking. Previous studies have shown that NOP-receptor activation reduces alcohol intake in genetically selected alcohol-preferring as well as alcohol-dependent rats. NOP activation also blocks stress- and cue-induced reinstatement of alcohol-seeking behavior.OBJECTIVES: Here, we aimed to examine a novel, potent, and brain-penetrant small-molecule NOP-receptor agonist, SR-8993, in animal models of alcohol- as well as anxiety-related behavior using male Wistar rats.RESULTS: SR-8993 was mildly anxiolytic when given to naïve animals and potently reversed acute alcohol withdrawal-induced ("hangover") anxiety. SR-8993 reduced both home-cage limited access drinking, operant responding for alcohol, and escalation induced through prolonged intermittent access to alcohol. SR-8993 further attenuated stress- as well as cue-induced relapse to alcohol seeking. For the effective dose (1.0 mg/kg), non-specific effects such as sedation may be limited, since a range of control behaviors were unaffected, and this dose did not interact with alcohol elimination.CONCLUSION: These findings provide further support for NOP-receptor agonism as a promising candidate treatment for alcoholism and establish SR-8993 or related molecules as suitable for further development as therapeutics.
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| 17. |
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| 18. |
- Bjartmar, Lisa, 1966-, et al.
(author)
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Selective effects on NGFI-A, MR, GR and NGFI-B hippocampal mRNA expression after chronic treatment with different subclasses of antidepressants in the rat
- 2000
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In: Psychopharmacology. - : Springer Science and Business Media LLC. - 0033-3158 .- 1432-2072. ; 151:1, s. 7-12
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Journal article (peer-reviewed)abstract
- There is a latency period of several weeks before the onset of clinical effect of antidepressant drugs. The detailed mechanisms underlying drug-induced adaptive neuronal changes are not known. To elucidate the involvement of changes in gene expression of candidate transcription factors, we treated rats for 21 days with buspirone, fluoxetine, 8-OH-DPAT and moclobemide. In situ hybridization was used to study mRNAs encoding NGFI-A, NGFI-B and the glucocorticoid receptors, MR and GR. NGFI-A mRNA expression increased profoundly in the hippocampal formation and the cerebral cortex after all drug treatments, especially after moclobemide treatment (77-122% increase), with the exception of buspirone. MR mRNA expression was induced in hippocampal CA1/CA2 subregions (27-37%) by all antidepressants, while moclobemide and 8-OH-DPAT significantly increased GR gene expression mainly in the CA1 region (31-44%). NGFI-B mRNA was significantly decreased in the hippocampal CA3 subfield (23%) and restrosplenial granular cortex (38%) by moclobemide treatment. There are selective effects of antidepressant drugs on specific transcription factors. These may be important for adaptive neuronal and neuroendocrine changes after antidepressant treatment including HPA axis negative feedback regulation.
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| 19. |
- Björk, Karl, et al.
(author)
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β-Arrestin 2 knockout mice exhibit sensitized dopamine release and increased reward in response to a low dose of alcohol
- 2013
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In: Psychopharmacology. - : Springer. - 0033-3158 .- 1432-2072. ; 230:3, s. 439-449
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Journal article (peer-reviewed)abstract
- RationaleThe rewarding effects of alcohol have been attributed to interactions between opioid and dopaminergic system within the mesolimbic reward pathway. We have previously shown that ablation of β-arrestin 2 (Arrb2), a crucial regulator of μ-opioid receptor function, attenuates alcohol-induced hyperlocomotion and c-fos activation in the nucleus accumbens.ObjectivesHere, we further investigated the role of Arrb2 in modulating alcohol-induced dopamine (DA) release and conditioned place preference (CPP). We also assessed the functional importance of Arrb2 for μ-opioid receptor surface expression and signaling following an acute alcohol challenge.MethodsAlcohol-evoked (0.375, 0.75, and 1.5 g/kg intraperitoneally) DA release was measured by in vivo microdialysis in the shell of nucleus accumbens. Reward was assessed by the CPP paradigm. Receptor function was assessed by μ-receptor binding and [35S]GTP-γ-S autoradiography.ResultsIn Arrb2 knockout mice accumbal DA levels reach maximum response at a lower dose compared to wild-type (wt) animals. In line with these results, Arrb2 knockout mice display increased CPP for alcohol as compared to wt mice. Finally, Arrb2 mutant mice display increased μ-opioid receptor signaling in the ventral and dorsal striatum and amygdala in response to a low dose of alcohol, indicating impaired desensitization mechanisms in these mice.ConclusionsOur results show that Arrb2 modulates the response to low doses of alcohol on various levels including μ-opioid receptor signaling, DA release, and reward. They also reveal a clear dissociation between the effects of Arrb2 on psychomotor and reward behaviors.
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| 20. |
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| 21. |
- Brooks, Samantha J., et al.
(author)
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The impact of cognitive training in substance use disorder : the effect of working memory training on impulse control in methamphetamine users
- 2017
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In: Psychopharmacology. - : Springer Science and Business Media LLC. - 0033-3158 .- 1432-2072. ; 234:12, s. 1911-1921
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Journal article (peer-reviewed)abstract
- OBJECTIVES: Impulsivity is a vulnerability trait for poor self-regulation in substance use disorder (SUD). Working memory (WM) training improves impulsivity and self-regulation in psychiatric disorders. Here we test WM training in methamphetamine use disorder (MUD).METHODS: There are 15 MUD patients receiving inpatient treatment as usual (TAU) and 20 who additionally completed WM cognitive training (CT) and 25 healthy controls (HC). MANCOVA repeated measures analyses examined changes in impulsivity and self-regulation at baseline and after 4 weeks.RESULTS: = 0.3523, p < 0.05). Compared to follow-up TAU, follow-up CT group had higher self-reported mood scores (t = 2.784, p = 0.01) and higher compared to CT baseline (t = 2.386, p = 0.036). Feelings of self-control were higher in CT than TAU at follow-up (t = 2.736, p = 0.012) and also compared to CT baseline (t = 3.390, p = 0.006), lack of planning significantly improved in CT between baseline and follow-up (t = 2.219, p = 0.048), as did total impulsivity scores (t = 2.085, p = 0.048). Measures of self-regulation were improved in the CT group compared to TAU at follow-up, in total score (t = 2.442, p = 0.038), receiving score (t = 2.314, p = 0.029) and searching score (t = 2.362, p = 0.027). Implementing self-regulation was higher in the CT group compared to TAU (t = 2.373, p = 0.026).CONCLUSIONS: WM training may improve control of impulsivity and self-regulation in people with MUD.
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| 22. |
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| 25. |
- Cippitelli, Andrea, et al.
(author)
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Neuropeptide Y (NPY) suppresses yohimbine-induced reinstatement of alcohol seeking
- 2010
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In: Psychopharmacology. - : Springer. - 0033-3158 .- 1432-2072. ; 208:3, s. 417-426
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Journal article (peer-reviewed)abstract
- INTRODUCTION: Reinstatement of responding to a previously alcohol-associated lever following extinction is an established model of relapse-like behavior and can be triggered by stress exposure. Here, we examined whether neuropeptide Y (NPY), an endogenous anti-stress mediator, blocks reinstatement of alcohol-seeking induced by the pharmacological stressor yohimbine.MATERIALS AND METHODS: NPY [5.0 or 10.0 mug/rat, intracerebroventricularly (ICV)] dose-dependently blocked the reinstatement of alcohol seeking induced by yohimbine (1.25 mg/kg, i.p.) but failed to significantly suppress the maintenance of alcohol self-administration. We then used c-fos expression mapping to examine neuronal activation following treatment with yohimbine or NPY alone or yohimbine following NPY pre-treatment.RESULTS AND DISCUSSION: The analysis was focused on a network of structures previously implicated in yohimbine-induced reinstatement, comprised of central (CeA) and basolateral (BLA) amygdala and the shell of the nucleus accumbens (Nc AccS). Within this network, both yohimbine and NPY potently induced neuronal activation, and their effects were additive, presumably indicating activation of excitatory and inhibitory neuronal populations, respectively.CONCLUSION: These results suggest that NPY selectively suppresses relapse to alcohol seeking induced by stressful events and support the NPY system as an attractive target for the treatment of alcohol addiction.
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| 26. |
- Cippitelli, Andrea, et al.
(author)
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Suppression of alcohol self-administration and reinstatement of alcohol seeking by melanin-concentrating hormone receptor 1 (MCH1-R) antagonism in Wistar rats
- 2010
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In: Psychopharmacology. - : Springer. - 0033-3158 .- 1432-2072. ; 211:4, s. 367-375
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Journal article (peer-reviewed)abstract
- RATIONALE: Melanin-concentrating hormone (MCH) is involved in regulation of appetitive behaviors as well as emotional reactivity and reward, behavioral domains relevant to alcohol addiction.MATERIALS AND METHODS: We evaluated the effects of the non-peptide MCH1 receptor antagonist, GW803430 [6-(4-chloro-phenyl)-3-[3-methoxy-4-(2-pyrrolidin-1-yl-ethoxy)-phenyl]-3H-thieno[3,2-d]pyrimidin-4-one; 3-30 mg/kg, i.p.] on alcohol-related behaviors in Wistar rats.RESULTS: Ex vivo binding experiments demonstrated that the GW803430 dose range used resulted in high central MCH1 receptor occupancy. Alcohol self-administration was dose-dependently and potently suppressed, by approximately 80% at the highest dose. Reinstatement of alcohol-seeking induced by alcohol-associated cues was essentially eliminated. In contrast, reinstatement induced by footshock stress was not significantly altered. Taste preference for a quinine/saccharin solution, locomotor activity, and alcohol elimination were unaffected.CONCLUSION: Together, these observations support a specific involvement of the MCH system in mediating alcohol reward and cue-induced relapse to alcohol seeking. MCH1-R antagonism may constitute an attractive treatment target for alcohol use disorders.
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| 27. |
- Collin Hasselbalch, Katharina, et al.
(author)
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Potential shortcomings in current studies on the effect of intranasal oxytocin in Anorexia Nervosa and healthy controls : A systematic review and meta-analysis
- 2020
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In: Psychopharmacology. - : Springer. - 0033-3158 .- 1432-2072. ; 237:10, s. 2891-2903
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Research review (peer-reviewed)abstract
- Rationale: The psychopathology of anorexia nervosa (AN) includes altered social cognition and information processing of fear and anxiety. Oxytocin, a neuromodulating hormone, may influence these functions and could be valuable for the treatment of AN.Objective: The current study aimed at reviewing the effect of intranasal oxytocin (IN-OT) on attentional bias (AB) and emotion recognition (ER) in AN.Methods: A systematic literature review was done for free-text and the MeSH-terms: anorexia nervosa, feeding and eating disorders, and oxytocin. Six publications, reporting from 4 unique clinical trials, were included in this review. A meta-analysis was conducted to examine the effects of IN-OT on AB towards food images and ER on healthy controls (HC) and patients with AN.Results: Overall, IN-OT did not influence AB towards food images (effect size = 0.20 [- 0.16, 0.57], p = 0.28) and had no effect on ER (effect size = - 0.01 [- 0.27, 0.26], p = 0.97) in patients with AN and healthy control (HC) subjects collectively. Assessing HC and AN separately in subgroup analyses did not show any significant effect on AB and ER in neither of the subgroups. All tests were done between 15 and 55 min post-administration of IN-OT, while peak concentration in the cerebrospinal fluid has been determined to be at 75 min.Conclusion: The current level of evidence is moderate showing no effect of IN-OT on AB or ER in AN. However, brain exposure may not have been sufficient which future studies with IN-OT need to ensure by considering dose and dose-to-task interval.
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| 28. |
- de Almeida, Rosa Maria M, et al.
(author)
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Heightened aggression after chronic flunitrazepam in male rats: potential links to cortical and caudate-putamen-binding sites.
- 2008
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In: Psychopharmacology. - : Springer Science and Business Media LLC. - 0033-3158 .- 1432-2072. ; 197:2, s. 309-18
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Journal article (peer-reviewed)abstract
- RATIONALE: Higher doses of benzodiazepines induce sedation. However, in low to moderate doses, benzodiazepines can increase aggressive behavior both after acute and chronic administration. The determinants for increasing aggression after chronic intake of flunitrazepam, a so-called date rape drug, in violence-prone individuals are incompletely understood. OBJECTIVES: The aim of this study is to assess the effects of acute and chronic treatment with flunitrazepam on male aggression in resident rats. We also examined possible changes in binding to benzodiazepine receptors throughout the brain of rats that display aggressive behavior after repeated flunitrazepam treatment using quantitative receptor autoradiography. MATERIALS AND METHODS: The behaviors of the male Wistar resident rats (n = 35) toward a male intruder were recorded for 10 min twice a week. The salient aggressive and non-aggressive elements in the resident rat's behavior were analyzed. Initially, the dose-dependent effects of flunitrazepam (0.01, 0.03, 0.1, 0.18, and 0.3 mg/kg) or vehicle were determined in all rats; subsequently, 0.3 mg/kg per day flunitrazepam was administered for 42 days (n = 15), and a parallel group was treated with vehicle (n = 20). After the chronic treatment, the flunitrazepam (0, 0.01, 0.03, 0.1, 0.18, and 0.3 mg/kg) effects were again assessed. RESULTS: The most significant finding is the escalation of aggression after chronic treatment with flunitrazepam. A previously sedative 0.3 mg/kg dose of flunitrazepam engendered very high levels of attack bites, sideways threats, and aggressive postures (total aggression) after 6 weeks of daily administration. Individual differences emerged, and these were associated with decreased binding to benzodiazepine receptors, mainly in the limbic structures such as the cingulate cortex (cingulate areas 1 and 2) and caudate-putamen (posterior part) of aggressive animals, suggesting that these areas are pivotal in the control of emotional and aggressive behavior. CONCLUSIONS: Chronic flunitrazepam produces changes in receptor binding in discrete areas of the cingulate cortex and caudate-putamen that are proposed to be part of the mechanisms for increased expression of aggressive behavior.
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| 29. |
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| 31. |
- Domi, Esi, et al.
(author)
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Further evidence for the involvement of the PPAR gamma system on alcohol intake and sensitivity in rodents
- 2020
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In: Psychopharmacology. - : Springer Science and Business Media LLC. - 0033-3158 .- 1432-2072. ; 237, s. 2983-2992
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Journal article (peer-reviewed)abstract
- Rationale Peroxisome Proliferator Activator receptors (PPARs) are intracellular receptors that function as transcription factors, which regulate specific metabolic and inflammatory processes. PPARs are broadly distributed in the body and are also expressed in the central nervous system, especially in areas involved in addiction-related behavioral responses. Recent studies support a role of PPARs in alcoholism and pioglitazone: a PPAR gamma agonist used for treatment of type 2 diabetes showed efficacy in reducing alcohol drinking, stress-induced relapse, and alcohol withdrawal syndrome in rats. Objectives and Methods In the current work, we tested the pharmacological effects of pioglitazone on binge-like alcohol consumption using an intermittent two-bottle choice paradigm in Wistar rats and on the "drinking in the dark" (DID) model in mice with selective deletion of PPAR gamma in neurons. Results Our data show that repeated administration of pioglitazone (10, 30 mg/kg) reduces high voluntary alcohol consumption in Wistar rats. Pre-treatment with the selective PPAR gamma antagonist GW9662 (5 mg/kg) completely prevented the effect of pioglitazone, demonstrating that its action is specifically mediated by activation of PPAR gamma. In line with this result, repeated administration of pioglitazone (30 mg/kg) attenuated binge alcohol consumption in PPAR gamma((+/+)) mice. Whereas in PPAR gamma((-/-)) mice, which exhibit reduced alcohol consumption, pioglitazone had no effect. Of note, PPAR gamma((-/-)) mice exhibited lower patterns of alcohol drinking without showing difference in sucrose (control) intake. Interestingly, PPAR gamma((-/-)) mice displayed a higher sensitivity to the sedative and ataxic effect of alcohol compared with their wild-type counterpart. Conclusions Collectively, these data suggest that PPAR gamma agonists, and specifically pioglitazone, could be potential therapeutics for the treatment of binge alcohol drinking.
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| 32. |
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| 33. |
- Ekström, Johan G., et al.
(author)
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Effects of blue light and caffeine on mood
- 2014
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In: Psychopharmacology. - : Springer Science and Business Media LLC. - 0033-3158 .- 1432-2072. ; 231:18, s. 3677-3683
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Journal article (peer-reviewed)abstract
- Both short wavelength (blue) light and caffeine have been studied for their mood enhancing effects on humans. The ability of blue light to increase alertness, mood and cognitive function via non-image forming neuropathways has been suggested as a non-pharmacological countermeasure for depression across a range of occupational settings. This experimental study compared blue light and caffeine and aimed to test the effects of blue light/placebo (BLU), white light/240-mg caffeine (CAF), blue light/240-mg caffeine (BCAF) and white light/placebo (PLA), on mood. A randomised, controlled, crossover design study was used, in a convenience population of 20 healthy volunteers. The participants rated their mood on the Swedish Core Affect Scales (SCAS) prior to and after each experimental condition to assess the dimensions of valence and activation. There was a significant main effect of light (p = 0.009), and the combination of blue light and caffeine had clear positive effects on core effects (ES, ranging from 0.41 to 1.20) and global mood (ES, 0.61 +/- 0.53). The benefits of the combination of blue light and caffeine should be further investigated across a range of applications due to the observed effects on the dimensions of arousal, valence and pleasant activation.
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| 34. |
- Engel, Jörgen, 1942, et al.
(author)
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Blockade of growth hormone secretagogue receptor 1A signaling by JMV 2959 attenuates the NMDAR antagonist, phencyclidine-induced impairments in prepulse inhibition
- 2015
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In: Psychopharmacology. - : Springer Science and Business Media LLC. - 0033-3158 .- 1432-2072. ; 232:23, s. 4285-4292
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Journal article (peer-reviewed)abstract
- Schizophrenic-spectrum patients commonly display deficits in preattentive information processing as evidenced, for example, by disrupted prepulse inhibition (PPI), a measure of sensorimotor gating. Similar disruptions in PPI can be induced in rodents and primates by the psychotomimetic drug phencyclidine (PCP), a noncompetitive inhibitor of the NMDA receptor. Mounting evidence suggests that the hunger hormone ghrelin and its constitutively active receptor influences neuronal circuits involved in the regulation of mood and cognition. In the present series of experiments, we investigated the effects of ghrelin and the growth hormone secretagogue receptor (GHS-R1A) neutral antagonist, JMV 2959, on acoustic startle responses (ASR), PPI, and PCP-induced alterations in PPI. Intraperitoneal (i.p.) administration of ghrelin (0.033, 0.1, and 0.33 mg/kg) did not alter the ASR or PPI in rats. Conversely, i.p. injection of JMV 2959 (1, 3, and 6 mg/kg), dose dependently decreased the ASR and increased PPI. Pretreatment with JMV 2959 at a dose with no effect on ASR or PPI per se, completely blocked PCP-induced (2 mg/kg) deficits in PPI while pretreatment with the highest dose of ghrelin did not potentiate or alter PPI responses of a sub-threshold dose of PCP (0.75 mg/kg). These findings indicate that the GHS-R1A is involved in specific behavioral effects of PCP and may have relevance for patients with schizophrenia.
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| 36. |
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| 37. |
- Fejgin, Kim, 1978, et al.
(author)
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The atypical antipsychotic, aripiprazole, blocks phencyclidine-induced disruption of prepulse inhibition in mice.
- 2007
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In: Psychopharmacology. - : Springer Science and Business Media LLC. - 0033-3158 .- 1432-2072. ; 191:2, s. 377-85
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Journal article (peer-reviewed)abstract
- RATIONALE: The psychotomimetic drug, phencyclidine, induces schizophrenia-like behavioural changes in both humans and animals. Phencyclidine-induced disruption of sensory motor gating mechanisms, as assessed by prepulse inhibition of the acoustic startle, is widely used in research animals as a screening model for antipsychotic properties in general and may predict effects on negative and cognitive deficits in particular. Dopamine (DA) stabilizers comprise a new generation of antipsychotics characterized by a partial DA receptor agonist or antagonist action and have been suggested to have a more favourable clinical profile. OBJECTIVE: The aim of the present study was to investigate the ability of first, second and third generation antipsychotics to interfere with the disruptive effect of phencyclidine on prepulse inhibition in mice. RESULTS: Aripiprazole blocked the phencyclidine-induced disruption of prepulse inhibition. The atypical antipsychotic clozapine was less effective, whereas olanzapine, and the typical antipsychotic haloperidol, failed to alter the effects of phencyclidine on prepulse inhibition. CONCLUSIONS: The somewhat superior efficacy of clozapine compared to haloperidol may be explained by its lower affinity and faster dissociation rate for DA D2 receptors possibly combined with an interaction with other receptor systems. Aripiprazole was found to be more effective than clozapine or olanzapine, which may be explained by a partial agonist activity of aripiprazole at DA D2 receptors. In conclusion, the present findings suggest that partial DA agonism leading to DA stabilizing properties may have favourable effects on sensorimotor gating and thus tentatively on cognitive dysfunctions in schizophrenia.
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- Frånberg, Olivia, et al.
(author)
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Asenapine, a novel psychopharmacologic agent : preclinical evidence for clinical effects in schizophrenia.
- 2008
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In: Psychopharmacology. - : Springer Science and Business Media LLC. - 0033-3158 .- 1432-2072. ; 196:3
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Journal article (peer-reviewed)abstract
- RATIONALE: Asenapine is a novel psychopharmacologic agent being developed for the treatment of schizophrenia and bipolar disorder.MATERIALS AND METHODS: The present study was undertaken to investigate the effects of asenapine using animal models predictive of antipsychotic efficacy (conditioned avoidance response [CAR]) and extrapyramidal side effects (EPS; catalepsy). In parallel, the effects of asenapine on regional dopamine output using in vivo microdialysis in freely moving rats, dopamine output in the core and shell subregions of nucleus accumbens (NAc) using in vivo voltammetry in anesthetized rats, and N-methyl-D: -aspartate (NMDA)-induced currents in pyramidal neurons of the medial prefrontal cortex (mPFC) using the electrophysiological technique intracellular recording in vitro were assessed.RESULTS: Asenapine (0.05-0.2 mg/kg, subcutaneous [s.c.]) induced a dose-dependent suppression of CAR (no escape failures recorded) and did not induce catalepsy. Asenapine (0.05-0.2 mg/kg, s.c.) increased dopamine efflux in both the mPFC and the NAc. Low-dose asenapine (0.01 mg/kg, intravenous [i.v.]) increased dopamine efflux preferentially in the shell compared to the core of NAc, whereas at a higher dose (0.05 mg/kg, i.v.), the difference disappeared. Finally, like clozapine (100 nM), but at a considerably lower concentration (5 nM), asenapine significantly potentiated the NMDA-induced responses in pyramidal cells of the mPFC.CONCLUSIONS: These preclinical data suggest that asenapine may exhibit highly potent antipsychotic activity with very low EPS liability. Its ability to increase both dopaminergic and glutamatergic activity in rat mPFC suggests that asenapine may possess an advantageous effect not only on positive symptoms in patients with schizophrenia, but also on negative and cognitive symptoms.
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- Ghersi, Marisa S, et al.
(author)
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Ghrelin increases memory consolidation through hippocampal mechanisms dependent on glutamate release and NR2B-subunits of the NMDA receptor
- 2015
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In: Psychopharmacology. - : Springer Science and Business Media LLC. - 0033-3158 .- 1432-2072. ; 232:10, s. 1843-1857
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Journal article (peer-reviewed)abstract
- RATIONALE: Ghrelin (Ghr) is a peptide that participates in the modulation of several biological processes. Ghr administration into the hippocampus improves learning and memory in different memory tests. However, the possible mechanisms underlying this effect on memory have not yet been clarified.OBJECTIVE: The purpose of the present work is to add new insights about the mechanisms by which Ghr modulates long-term memory consolidation in the hippocampus. We examined Ghr effects upon processes related to increased synaptic efficacy as presynaptic glutamate release and changes in the expression of the NR2B-subunits containing n-methyl-d-aspartate receptors (NMDAR), which are critical for LTP induction. We also attempted to determine the temporal window in which Ghr administration induces memory facilitation and if the described effects depend on GHS-R1a stimulation.RESULTS: The present research demonstrated that Ghr increased glutamate release from hippocampal synaptosomes; intra-hippocampal Ghr administration increased NR2B-subunits expression in CA1 and DG subareas and also reversed the deleterious effects of the NR2B-subunit-specific antagonist, Ro 25-6981, upon memory consolidation and LTP generation in the hippocampus. These effects are likely to be the consequence of GHS-R1a activation.CONCLUSION: According to the results above mentioned and previous findings, we can hypothesize some of the mechanisms by which Ghr modulates memory consolidation. At presynaptic level, Ghr stimulates glutamate release, probably by enhancing [Ca(2+)]i. At postsynaptic level, the glutamate released activates NMDAR while Ghr also mediates effects directly activating its specific receptors and increases NR2B-subunit expression.
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- Granholm, Linnea, et al.
(author)
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Impact of adolescent ethanol exposure and adult amphetamine self-administration on evoked striatal dopamine release in male rats
- 2015
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In: Psychopharmacology. - : Springer Science and Business Media LLC. - 0033-3158 .- 1432-2072. ; 232:24, s. 4421-4431
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Journal article (peer-reviewed)abstract
- Adolescent binge drinking is common and associated with increased risk of substance use disorders. Transition from recreational to habitual ethanol consumption involves alterations in dorsal striatal function, but the long-term impact of adolescent ethanol exposure upon this region remains unclear. This study aimed to characterise and describe relationships between adolescent ethanol exposure, amphetamine self-administration and adult dopamine dynamics in dorsal striatum, including response to amphetamine challenge, in male Wistar rats. Ethanol (2 g/kg) or water was administered intragastrically in an episodic binge-like regimen (three continuous days/week) between 4 and 9 weeks of age (i.e. post-natal days 28-59). In adulthood, animals were divided into two groups. In the first, dorsal striatal potassium-evoked dopamine release was examined via chronoamperometry, in the basal state and after a single amphetamine challenge (2 mg/kg, i.v.). In the second, amphetamine self-administration behaviour was studied (i.e. fixed and progressive ratio) before chronoamperometric analysis was conducted as described above. Adolescent ethanol exposure suppressed locally evoked dopamine response after amphetamine challenge in adulthood, whereas in the basal state, no differences in dopamine dynamics were detected. Ethanol-exposed animals showed no differences in adult amphetamine self-administration behaviour but an abolished effect on dopamine removal in response to a single amphetamine challenge after self-administration. Amphetamine challenges in adult rats revealed differences in in vivo dopamine function after adolescent ethanol exposure. The attenuated drug response in ethanol-exposed animals may affect habit formation and contribute to increased risk for substance use disorders as a consequence of adolescent ethanol.
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- Guitart-Masip, Marc, et al.
(author)
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Differential, but not opponent, effects of L-DOPA and citalopram on action learning with reward and punishment
- 2014
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In: Psychopharmacology. - : Springer Science and Business Media LLC. - 0033-3158 .- 1432-2072. ; 231:5, s. 955-966
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Journal article (peer-reviewed)abstract
- Decision-making involves two fundamental axes of control namely valence, spanning reward and punishment, and action, spanning invigoration and inhibition. We recently exploited a go/no-go task whose contingencies explicitly decouple valence and action to show that these axes are inextricably coupled during learning. This results in a disadvantage in learning to go to avoid punishment and in learning to no-go to obtain a reward. The neuromodulators dopamine and serotonin are likely to play a role in these asymmetries: Dopamine signals anticipation of future rewards and is also involved in an invigoration of motor responses leading to reward, but it also arbitrates between different forms of control. Conversely, serotonin is implicated in motor inhibition and punishment processing. To investigate the role of dopamine and serotonin in the interaction between action and valence during learning. We combined computational modeling with pharmacological manipulation in 90 healthy human volunteers, using levodopa and citalopram to affect dopamine and serotonin, respectively. We found that, after administration of levodopa, action learning was less affected by outcome valence when compared with the placebo and citalopram groups. This highlights in this context a predominant effect of levodopa in controlling the balance between different forms of control. Citalopram had distinct effects, increasing participants' tendency to perform active responses independent of outcome valence, consistent with a role in decreasing motor inhibition. Our findings highlight the rich complexities of the roles played by dopamine and serotonin during instrumental learning.
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