WFRF:(Sommer Wolfgang H)
Sökning: WFRF:(Sommer Wolfgang H) > β-Arrestin 2 knocko...
β-Arrestin 2 knockout mice exhibit sensitized dopamine release and increased reward in response to a low dose of alcohol
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- Björk, Karl (författare)
- Karolinska Institutet
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- Tronci, Valeria (författare)
- Psychobiology Section, NIDA, National Institutes of Health, Baltimore, MD, USA
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- Thorsell, Annika (författare)
- Linköpings universitet,Avdelningen för neuro- och inflammationsvetenskap,Medicinska fakulteten,Centrum för social och affektiv neurovetenskap (CSAN)
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- 2013-06-19
- 2013
- Engelska.
- Ingår i: Psychopharmacology. - : Springer. - 0033-3158 .- 1432-2072. ; 230:3, s. 439-449
- Tidskriftsartikel (refereegranskat)
Abstract
Ämnesord
Stäng
- 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.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Neurovetenskaper (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Neurosciences (hsv//eng)
Nyckelord
- arrestin
- conditioned place preference
- dopamine
- reward
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- Björk, Karl
- Tronci, Valeria
- Thorsell, Annika
- Tanda, Gianluigi
- Hirth, Natalie
- Heilig, Markus
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- Hansson, Anita C ...
- Sommer, Wolfgang ...
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