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Dopamine transporter gene expression within the nucleus accumbens plays important role in the acquisition and reinstatement of ethanol-seeking behavior in mice.

Abstract：

:Alcoholism and alcohol use disorders are chronically relapsing conditions which is a major problem in treating alcohol addiction. In a previous study we showed that the dopamine transporter (DAT) is implicated in voluntary intake and preference. However, its role in modulating ethanol-associated contextual memory remains largely unknown. In this study we have investigated the role of DAT in ethanol-induced conditioned place preference (EtOH-CPP) acquisition and reinstatement in adult male C57BL/6 mice. For this purpose, we used both loss- and gain-of-function approaches to test the effects of central DAT manipulation on EtOH-CPP. We developed a lentiviral-mediated gene transfer approach to examine whether DAT knockdown (shDAT) or overexpression in the nucleus accumbens (Nacc) is enough to impair EtOH-CPP acquisition and reinstatement. In the first experiment, results showed that DAT knockdown blocked, whereas DAT overexpression, exacerbated the acquisition of EtOH-CPP. In the second experiment and after the EtOH-CPP expression, the mice were subjected to a 14-day extinction trials before drug-induced EtOH-CPP reinstatement was induced by a priming injection of 1 g/kg EtOH. Results indicated that reinstatement of EtOH-CPP was considerably decreased after accumbal shDAT injection. However, DAT overexpression significantly increased EtOH-CPP reinstatement. Finally, and following DAT mRNA quantification using RT-PCR, Pearson's correlation showed a strong positive relationship between accumbal DAT mRNA and EtOH-CPP acquisition and reinstatement. These results suggest that DAT expression in the Nacc is involved in the acquisition and retrieval of EtOH contextual memory and that blockade of this transporter can decrease the rewarding properties of EtOH.

journal_name

Behav Brain Res

journal_title

Behavioural brain research

authors

Bahi A

doi

10.1016/j.bbr.2020.112475

subject

Has Abstract

pub_date

2020-03-02 00:00:00

pages

112475

eissn

0166-4328

issn

1872-7549

pii

S0166-4328(19)31550-5

journal_volume

381

pub_type

杂志文章

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Dopamine transporter gene expression within the nucleus accumbens plays important role in the acquisition and reinstatement of ethanol-seeking behavior in mice.