| 1. |
- Azadi, Maryam, et al.
(författare)
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Preconception paternal morphine exposure leads to an impulsive phenotype in male rat progeny
- 2021
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Ingår i: Psychopharmacology. - : Springer Nature. - 0033-3158 .- 1432-2072. ; 238, s. 3435-3446
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Tidskriftsartikel (refereegranskat)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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| 2. |
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| 3. |
- Collin Hasselbalch, Katharina, et al.
(författare)
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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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Ingår i: Psychopharmacology. - : Springer. - 0033-3158 .- 1432-2072. ; 237:10, s. 2891-2903
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Forskningsöversikt (refereegranskat)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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| 4. |
- Domi, Esi, et al.
(författare)
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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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Ingår i: Psychopharmacology. - : Springer Science and Business Media LLC. - 0033-3158 .- 1432-2072. ; 237, s. 2983-2992
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Tidskriftsartikel (refereegranskat)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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| 5. |
- Kalafateli, Aimilia Lydia, 1987, et al.
(författare)
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Effects of sub-chronic amylin receptor activation on alcohol-induced locomotor stimulation and monoamine levels in mice
- 2020
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Ingår i: Psychopharmacology. - : Springer Science and Business Media LLC. - 0033-3158 .- 1432-2072. ; 237, s. 3249-3257
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Tidskriftsartikel (refereegranskat)abstract
- Rationale Amylin receptors consist of the calcitonin receptor (CTR) and one of three receptor activity-modifying proteins (RAMPs). The identification of amylin receptors in areas processing reward, namely laterodorsal tegmental area (LDTg), ventral tegmental area (VTA), and nucleus accumbens (NAc), has attributed them a role as reward regulators. Indeed, acute activation of amylin receptors by the amylin receptor agonist salmon calcitonin (sCT) attenuates alcohol-induced behaviours in rodents. Objectives The effects of long-term administration of sCT on alcohol-related behaviours and the molecular mechanisms underlying these processes are not yet elucidated. To fill this knowledge gap, we investigated the effects of sub-chronic sCT treatment on the locomotor stimulatory responses to alcohol in mice and the molecular pathways involved. Methods We assessed the behavioural effects of sub-chronic sCT treatment by means of locomotor activity experiments in mice. We used western blot to identify changes of the CTR levels and ex vivo biochemical analysis to detect changes in monoamines and their metabolites. Results After discontinuation for 5 days of sCT treatment, alcohol did not induce locomotor stimulation in mice pre-treated with sCT when compared with vehicle, without altering secondary behavioural parameters of the locomotor activity experiment or the protein levels of the CTR in reward-related areas in the same set of animals. Moreover, repeated sCT treatment altered monoaminergic neurotransmission in various brain areas, including increased serotonin and decreased dopamine turnover in the VTA. Lastly, we identified a differential effect of repeated sCT and acute alcohol administration on alcohol-induced locomotion in mice, where sCT initially attenuated and later increased this alcohol response. It was further found that this treatment combination did not affect secondary behavioural parameters measured in this locomotor activity experiments. Conclusions These data suggest that sub-chronic sCT treatment differentially alters the ability of alcohol to cause locomotor stimulation, possibly through molecular mechanisms involving various neurotransmitter systems and not the CTR levels per se.
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| 6. |
- Mindthoff, A., et al.
(författare)
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No evidence that low levels of intoxication at both encoding and retrieval impact scores on the Gudjonsson Suggestibility Scale
- 2021
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Ingår i: Psychopharmacology. - : Springer Science and Business Media LLC. - 0033-3158 .- 1432-2072. ; 238:6, s. 1633-1644
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Tidskriftsartikel (refereegranskat)abstract
- Rationale It is not uncommon for police to question alcohol-intoxicated witnesses and suspects; yet, the full extent to which intoxication impacts individuals' suggestibility in the investigative interviewing context remains unclear. Objective The present study sought to measure the effect of alcohol-intoxication on interviewee suggestibility by implementing a standardized suggestibility test with participants whose intoxication-state was the same at both encoding and recall. Methods We randomly assigned participants (N = 165) to an intoxicated (mean breath alcohol level [BrAC] at encoding = 0.06%, and BrAC at retrieval = 0.07%), active placebo (participants believed they consumed alcohol but only consumed an insignificant amount to enhance believability), or control (participants knowingly remained sober) group. An experimenter then implemented the Gudjonsson Suggestibility Scale (GSS), which produced free recall outcomes (number of correct details and memory confabulations) and suggestibility outcomes (yielding to leading questions and changing answers in response to negative feedback from the experimenter). Results Intoxicated participants recalled fewer correct details than did placebo and control participants but did not make more confabulation errors. No effects of intoxication on suggestibility measures emerged. Conclusions Moderately intoxicated interviewees may not be more suggestible during investigative interviews than sober interviewees. However, before concrete evidence-based policy recommendations are made to law enforcement, further research is needed examining the effects of alcohol on suggestibility in conditions that are more reflective of the legal context.
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| 7. |
- Perini, Irene, et al.
(författare)
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Modeling social cognition in alcohol use disorder: lessons from schizophrenia
- 2024
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Ingår i: Psychopharmacology. - : SPRINGER. - 0033-3158 .- 1432-2072.
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Tidskriftsartikel (refereegranskat)abstract
- A better understanding of social deficits in alcohol use disorder (AUD) has the potential to improve our understanding of the disorder. Clinical research shows that AUD is associated with interpersonal problems and the loss of a social network which impedes response to treatment. Translational research between animal models and clinical research may benefit from a discussion of the models and methods that currently guide research into social cognition in AUD. We propose that research in AUD should harness recent technological developments to improve ecological validity while maintaining experimental control. Novel methods allow us to parse naturalistic social cognition into tangible components, and to investigate previously neglected aspects of social cognition. Furthermore, to incorporate social cognition as a defining element of AUD, it is critical to clarify the timing of these social disturbances. Currently, there is limited evidence to distinguish factors that influence social cognition as a consequence of AUD, and those that precede the onset of the disorder. Both increasing the focus on operationalization of social cognition into objective components and adopting a perspective that spans the clinical spectrum will improve our understanding in humans, but also possibly increase methodological consistency and translational dialogue across species. This commentary underscores current challenges and perspectives in this area of research.
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| 8. |
- Schwandt, Melanie L., et al.
(författare)
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PPAR gamma activation by pioglitazone does not suppress cravings for alcohol, and is associated with a risk of myopathy in treatment seeking alcohol dependent patients: a randomized controlled proof of principle study
- 2020
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Ingår i: Psychopharmacology. - : SPRINGER. - 0033-3158 .- 1432-2072. ; 237, s. 2367-2380
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Tidskriftsartikel (refereegranskat)abstract
- Rationale Proinflammatory processes have been implicated in alcohol addiction, craving, and relapse, while studies in experimental animals have suggested that activation of peroxisome proliferator-activated receptor gamma (PPAR gamma) inhibits proinflammatory signaling. Accordingly, it is hypothesized that medications with PPAR gamma activity may have therapeutic potential in alcohol dependence. Objectives We conducted a double-blind, placebo-controlled mechanistic proof of principle study in alcohol-dependent inpatients to investigate the effect of pioglitazone on alcohol craving. Methods Participants were treated for withdrawal, if needed, and then randomized to pioglitazone (target dose 45 mg/day) or placebo. Once at target dose, they completed two experimental manipulations: guided imagery, which used personalized auditory scripts to induce alcohol cravings, and a low-dose challenge with i.v. lipopolysaccharide (LPS; 0.8 ng/kg) or placebo, on two separate sessions, in counterbalanced order. Behavioral and endocrine responses as well as CSF levels of proinflammatory cytokines were evaluated. Results The study was prematurely terminated after randomization of 16 subjects, following an independent review that established a high risk of myopathy in the active treatment group. Analysis of those who completed the study indicated that pioglitazone was associated with elevated, rather than suppressed alcohol cravings in response to alcohol-associated stimuli. LPS did not induce cravings for alcohol and thus did not lend itself to evaluating pioglitazone effects; however, pioglitazone increased the neuroendocrine stress response to LPS. CSF levels of IL-6, TNF-alpha, or MCP-1 were unaffected by pioglitazone treatment. Conclusions Both safety and efficacy biomarker data suggest that pioglitazone lacks potential as a medication for the treatment of alcohol dependence.
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| 9. |
- Simonsson, Otto, et al.
(författare)
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Psychedelic use and psychiatric risks
- 2023
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Ingår i: Psychopharmacology. - : SPRINGER. - 0033-3158 .- 1432-2072.
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Tidskriftsartikel (refereegranskat)abstract
- RationaleResearch on psychedelics has recently shown promising results in the treatment of various psychiatric disorders, but relatively little remains known about the psychiatric risks associated with naturalistic use of psychedelics.ObjectiveThe objective of the current study was to investigate associations between naturalistic psychedelic use and psychiatric risks.MethodsUsing a sample representative of the US adult population with regard to sex, age, and ethnicity (N=2822), this study investigated associations between lifetime naturalistic psychedelic use, lifetime unusual visual experiences, and past 2-week psychotic symptoms.ResultsAmong respondents who reported lifetime psychedelic use (n=613), 1.3% reported having been told by a doctor or other medical professional that they had hallucinogen persisting perception disorder. In covariate-adjusted linear regression models, lifetime psychedelic use was associated with more unusual visual experiences at any point across the lifetime, but no association was observed between lifetime psychedelic use and past 2-week psychotic symptoms. There was an interaction between lifetime psychedelic use and family (but not personal) history of psychotic or bipolar disorders on past 2-week psychotic symptoms such that psychotic symptoms were highest among respondents who reported lifetime psychedelic use and a family history of psychotic or bipolar disorders and lowest among those who reported lifetime psychedelic use and no family history of psychotic or bipolar disorders.ConclusionsAlthough the results in this study should be interpreted with caution, the findings suggest that lifetime naturalistic use of psychedelics might be associated with more unusual visual experiences across the lifetime, as well as more psychotic symptoms in the past 2 weeks for individuals with a family history of psychotic or bipolar disorders and the reverse for those without such a family history. Future research should distinguish between different psychotic and bipolar disorders and should also utilize other research designs (e.g., longitudinal) and variables (e.g., polygenic risk scores) to better understand potential cause-and-effect relationships.
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| 10. |
- Tabrisi, Reza, 1982-, et al.
(författare)
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Clozapine but not lithium reverses aberrant tyrosine uptake in patients with bipolar disorder
- 2023
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Ingår i: Psychopharmacology. - : Springer. - 0033-3158 .- 1432-2072. ; 240:8, s. 1667-1676
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Tidskriftsartikel (refereegranskat)abstract
- RATIONALE: Availability of the dopamine and noradrenaline precursor tyrosine is critical for normal functioning, and deficit in tyrosine transport across cell membrane and the blood-brain barrier has been reported in bipolar disorder and schizophrenia. Clozapine and lithium are two psychoactive agents used to treat psychosis, mood disorders and suicidal behavior, but their mechanism of action remains largely unknown.OBJECTIVE: To characterize immediate and delayed differences in tyrosine uptake between healthy controls (HC) and bipolar patients (BP) and see if these differences could be normalized by either clozapine, lithium or both. A second objective was to see if clozapine and lithium have additive, antagonistic or synergistic effects in this.METHOD: Fibroblasts from five HC and five BP were incubated for 5 min or 6 h with clozapine, lithium, or combination of both. Radioactive labelled tyrosine was used to quantify tyrosine membrane transport.RESULTS: There was significantly reduced tyrosine uptake at baseline in BP compared to HC, a deficit that grew with increasing incubation time. Clozapine selectively increased tyrosine uptake in BP and abolished the deficit seen under baseline conditions, while lithium had no such effect. Combination treatment with clozapine and lithium was less effective than when clozapine was used alone.CONCLUSIONS: There was significant deficit in tyrosine transport in BP compared to HC that was reversed by clozapine but not lithium. Clozapine was more effective when used alone than when added together with lithium. Potential clinical implications of this will be discussed.
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