| 1. |
- Adermark, Louise, 1974, et al.
(författare)
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Acute and chronic modulation of striatal endocannabinoid-mediated plasticity by nicotine.
- 2019
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Ingår i: Addiction biology. - : Wiley. - 1369-1600 .- 1355-6215. ; 24:3, s. 355-363
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Tidskriftsartikel (refereegranskat)abstract
- The endocannabinoid (eCB) system modulates several phenomena related to addictive behaviors, and drug-induced changes in eCB signaling have been postulated to be important mediators of physiological and pathological reward-related synaptic plasticity. Here, we studied eCB-mediated long-term depression (eCB-LTD) in the dorsolateral striatum, a brain region critical for acquisition of habitual and automatic behavior. We report that nicotine differentially affects ex vivo eCB signaling depending on previous exposure in vivo. In the nicotine-naïve brain, nicotine facilitates eCB-signaling and LTD, whereas tolerance develops to this facilitating effect after subchronic exposure in vivo. In the end, a progressive impairment of eCB-induced LTD is established after protracted withdrawal from nicotine. Endocannabinoid-LTD is reinstated 6months after the last drug injection, but a brief period of nicotine re-exposure is sufficient to yet again impair eCB-signaling. LTD induced by the cannabinoid 1 receptor agonist WIN55,212-2 is not affected, suggesting that nicotine modulates eCB production or release. Nicotine-induced facilitation of eCB-LTD is occluded by the dopamine D2 receptor agonist quinpirole, and by the muscarinic acetylcholine receptor antagonist scopolamine. In addition, the same compounds restore eCB-LTD during protracted withdrawal. Nicotine may thus modulate eCB-signaling by affecting dopaminergic and cholinergic neurotransmission in a long-lasting manner. Overall, the data presented here suggest that nicotine facilitates eCB-LTD in the initial phase, which putatively could promote neurophysiological and behavioral adaptations to the drug. Protracted withdrawal, however, impairs eCB-LTD, which may influence or affect the ability to maintain cessation.
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| 2. |
- Badiani, Aldo, et al.
(författare)
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Comments: Addiction research and theory: a commentary on the Surgeon Generals Report on alcohol, drugs, and health
- 2018
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Ingår i: Addiction Biology. - : John Wiley & Sons. - 1355-6215 .- 1369-1600. ; 23:1, s. 3-5
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- The Office of the Surgeon General recently produced its first Report on the consequences of alcohol and drug abuse on health, making several very laudable policy recommendations. The Report also emphasizes the importance of adequate funding for biomedical research, which is good news for both researchers and patients. However, the Report is marred by a biased viewpoint on the psychology and neurobiology of drug addiction. We highlight here four controversial issues that were depicted as facts in the Report, thereby potentially misleading non-expert readers about the current state-of-the-art understanding of the psychology and neurobiology of drug addiction. It will be important to recognize a fuller range of scientific viewpoints in addiction neuroscience to avoid amplifying this bias in the coming years.
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| 3. |
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| 4. |
- Egecioglu, Emil, 1977, et al.
(författare)
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The role of ghrelin signalling for sexual behaviour in male mice.
- 2016
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Ingår i: Addiction biology. - : Wiley. - 1369-1600 .- 1355-6215. ; 21:2, s. 348-59
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Tidskriftsartikel (refereegranskat)abstract
- Ghrelin, a gut-brain signal, is well known to regulate energy homeostasis, food intake and appetite foremost via hypothalamic ghrelin receptors (GHS-R1A). In addition, ghrelin activates the reward systems in the brain, namely the mesolimbic dopamine system, and regulates thereby the rewarding properties of addictive drugs as well as of palatable foods. Given that the mesolimbic dopamine system mandates the reinforcing properties of addictive drugs and natural rewards, such as sexual behaviour, we hypothesize that ghrelin plays an important role for male sexual behaviour, a subject for the present studies. Herein we show that ghrelin treatment increases, whereas pharmacological suppression (using the GHSR-1A antagonist JMV2959) or genetic deletion of the GHS-R1A in male mice decreases the sexual motivation for as well as sexual behaviour with female mice in oestrus. Pre-treatment with L-dopa (a dopamine precursor) prior to treatment with JMV2959 significantly increased the preference for female mouse compared with vehicle treatment. On the contrary, treatment with 5-hydroxythyptohan (a precursor for serotonin) prior to treatment with JMV2959 decreased the sexual motivation compared to vehicle. In separate experiments, we show that ghrelin and GHS-R1A antagonism do not affect the time spent over female bedding as measured in the androgen-dependent bedding test. Collectively, these data show that the hunger hormone ghrelin and its receptor are required for normal sexual behaviour in male mice and that the effects of the ghrelin signalling system on sexual behaviour involve dopamine neurotransmission.
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| 5. |
- Feltmann, K., et al.
(författare)
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The monoamine stabilizer (-)-OSU6162 counteracts downregulated dopamine output in the nucleus accumbens of long-term drinking Wistar rats
- 2016
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Ingår i: Addiction Biology. - : Wiley. - 1355-6215 .- 1369-1600. ; 21:2, s. 438-449
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Tidskriftsartikel (refereegranskat)abstract
- We recently established that the monoamine stabilizer (-)-OSU6162 (OSU6162) decreased voluntary alcohol-mediated behaviors, including alcohol intake and cue/priming-induced reinstatement, in long-term drinking rats, while blunting alcohol-induced dopamine output in the nucleus accumbens (NAc) of alcohol-naive rats. Therefore, we hypothesized that OSU6162 attenuates alcohol-mediated behaviors by blunting alcohol's rewarding effects. Here, we evaluated the effects of long-term drinking and OSU6162 treatment (30mg/kg, sc) on basal and alcohol-induced (2.5g/kg, ip) NAc dopamine outputs in Wistar rats after 10months of intermittent access to 20% alcohol. The results showed that basal and alcohol-induced NAc dopamine outputs were significantly lower in long-term drinking rats, compared with alcohol-naive rats. In the long-term drinking rats, OSU6162 slowly increased and maintained the dopamine output significantly elevated compared with baseline for at least 4hours. Furthermore, OSU6162 pre-treatment did not blunt the alcohol-induced output in the long-term drinking rats, a finding that contrasted with our previous results in alcohol-naive rats. Finally, OSU6162 did not induce conditioned place preference (CPP) in either long-term drinking or alcohol-naive rats, indicating that OSU6162 has no reinforcing properties. To verify that the CPP results were not due to memory acquisition impairment, we demonstrated that OSU6162 did not affect novel object recognition. In conclusion, these results indicate that OSU6162 attenuates alcohol-mediated behaviors by counteracting NAc dopamine deficits in long-term drinking rats and that OSU6162 is not rewarding on its own. Together with OSU6162's beneficial side-effect profile, the present study merits evaluation of OSU6162's clinical efficacy to attenuate alcohol use in alcohol-dependent patients.
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| 6. |
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| 7. |
- Jonsson, Susanne, 1980, et al.
(författare)
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Involvement of lateral septum in alcohol's dopamine-elevating effect in the rat
- 2017
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Ingår i: Addiction Biology. - : Wiley. - 1355-6215 .- 1369-1600. ; 22:1, s. 93-102
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Tidskriftsartikel (refereegranskat)abstract
- Drugs of abuse share the ability to increase extracellular dopamine (DA) levels in the mesolimbic DA system. This effect has been linked to positive and reinforcing experiences of drug consumption and is presumed to be of importance for continued use, as well as for the development of dependence and addiction. Previous rat studies from our lab have implicated a neuronal circuitry involving glycine receptors in nucleus accumbens (nAc) and, secondarily, nicotinic acetylcholine receptors in the ventral tegmental area (VTA) in ethanol's (EtOH) DA-elevating effect. The work presented here, performed in male Wistar rats, suggests that the lateral septum (LS), which has previously been associated with different aspects of EtOH-related behaviour, is involved as well. In vivo microdialysis methodology demonstrated that blocking the generation of action potentials in LS using tetrodotoxin prevented a DA increase in nAc after accumbal EtOH perfusion. Retrograde tracing and polymerase chain reaction (PCR) were used to identify and characterize cells projecting to VTA from nAc/LS and from LS to nAc. Based on the PCR results, cells projecting from both LS/nAc to anterior VTA and from LS to nAc were mainly GABAergic neurons expressing glycine receptors, and these cells are presumed to be involved in mediating the DA-elevating effect of EtOH. These results provide further evidence implicating LS in the reinforcing effects of EtOH. Additional studies are needed to investigate LS involvement in EtOH consumption behaviour and its potential role in the development of dependence and addiction.
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| 8. |
- Kalafateli, Aimilia Lydia, 1987, et al.
(författare)
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Activation of amylin receptors attenuates alcohol-mediated behaviours in rodents.
- 2019
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Ingår i: Addiction biology. - : Wiley. - 1369-1600 .- 1355-6215. ; 24:3, s. 388-402
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Tidskriftsartikel (refereegranskat)abstract
- Alcohol expresses its reinforcing properties by activating areas of the mesolimbic dopamine system, which consists of dopaminergic neurons projecting from the ventral tegmental area to the nucleus accumbens. The findings that reward induced by food and addictive drugs involve common mechanisms raise the possibility that gut-brain hormones, which control appetite, such as amylin, could be involved in reward regulation. Amylin decreases food intake, and despite its implication in the regulation of natural rewards, tenuous evidence support amylinergic mediation of artificial rewards, such as alcohol. Therefore, the present experiments were designed to investigate the effect of salmon calcitonin (sCT), an amylin receptor agonist and analogue of endogenous amylin, on various alcohol-related behaviours in rodents. We showed that acute sCT administration attenuated the established effects of alcohol on the mesolimbic dopamine system, particularly alcohol-induced locomotor stimulation and accumbal dopamine release. Using the conditioned place preference model, we demonstrated that repeated sCT administration prevented the expression of alcohol's rewarding properties and that acute sCT administration blocked the reward-dependent memory consolidation. In addition, sCT pre-treatment attenuated alcohol intake in low alcohol-consuming rats, with a more evident decrease in high alcohol consumers in the intermittent alcohol access model. Lastly, sCT did not alter peanut butter intake, blood alcohol concentration and plasma corticosterone levels in mice. Taken together, the present data support that amylin signalling is involved in the expression of alcohol reinforcement and that amylin receptor agonists could be considered for the treatment of alcohol use disorder in humans.
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| 9. |
- Karlsson, Camilla, 1977-, et al.
(författare)
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Proinflammatory signaling regulates voluntary alcohol intake and stress-induced consumption after exposure to social defeat stress in mice
- 2017
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Ingår i: Addiction Biology. - : John Wiley & Sons. - 1355-6215 .- 1369-1600. ; 22:5, s. 1279-1288
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Tidskriftsartikel (refereegranskat)abstract
- Proinflammatory activity has been postulated to play a role in addictive processes and stress responses, but the underlying mechanisms remain largely unknown. Here, we examined the role of interleukin 1 (IL-1) and tumor necrosis factor-a (TNF-a) in regulation of voluntary alcohol consumption, alcohol reward and stress-induced drinking. Mice with a deletion of the IL-1 receptor I gene (IL-1RI KO) exhibited modestly decreased alcohol consumption. However, IL-1RI deletion affected neither the rewarding properties of alcohol, measured by conditioned place preference (CPP), nor stress-induced drinking induced by social defeat stress. TNF-a signaling can compensate for phenotypic consequences of IL1-RI deletion. We therefore hypothesized that double deletion of both IL-1RI and TNF-1 receptors (TNF-1R) may reveal the role of these pathways in regulation of alcohol intake. Double KOs consumed significantly less alcohol than control mice over a range of alcohol concentrations. The combined deletion of TNF-1R and IL-1RI did not influence alcohol reward, but did prevent increased alcohol consumption resulting from exposure to repeated bouts of social defeat stress. Taken together, these data indicate that IL-1RI and TNF-1R contribute to regulation of stress-induced, negatively reinforced drinking perhaps through overlapping signaling events downstream of these receptors, while leaving rewarding properties of alcohol largely unaffected.
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