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β-Arrestin 2 knockout mice exhibit sensitized dopamine release and increased reward in response to a low dose of alcohol
Karolinska Institute, Stockholm, Sweden .
Psychobiology Section, NIDA, National Institutes of Health, Baltimore, MD, USA .
Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för neuro- och inflammationsvetenskap. Linköpings universitet, Medicinska fakulteten. (Centrum för social och affektiv neurovetenskap (CSAN))
Psychobiology Section, NIDA, National Institutes of Health, Baltimore, MD, USA .
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2013 (Engelska)Ingår i: Psychopharmacology, ISSN 0033-3158, E-ISSN 1432-2072, Vol. 230, nr 3, s. 439-449Artikel i tidskrift (Refereegranskat) Published
Abstract [en]

Rationale

The 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.

Objectives

Here, 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.

Methods

Alcohol-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.

Results

In 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.

Conclusions

Our 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.

Ort, förlag, år, upplaga, sidor
Springer, 2013. Vol. 230, nr 3, s. 439-449
Nyckelord [en]
arrestin, conditioned place preference, dopamine, reward
Nationell ämneskategori
Neurovetenskaper
Identifikatorer
URN: urn:nbn:se:liu:diva-94653DOI: 10.1007/s00213-013-3166-xISI: 000327090500010PubMedID: 23779257OAI: oai:DiVA.org:liu-94653DiVA, id: diva2:634186
Tillgänglig från: 2013-06-28 Skapad: 2013-06-28 Senast uppdaterad: 2018-01-11Bibliografiskt granskad

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Thorsell, AnnikaHeilig, Markus

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