CD81, a member of the
tetraspanin family, plays important roles in many physiological processes, such as cell motility, attachment, and entry. Yet, CD81 functions in the brain remain unclear. In this study, we investigated the effects of CD81 knockdown, using lentiviral vectors (LV), on anxiety- and
ethanol-related behaviors. For this purpose, mice were stereotaxically injected with CD81
shRNA-expressing LV into the nucleus accumbens (Nacc) and were assessed for anxiety-like behavior using the elevated plus maze (EPM) and open field (OF) tests. Alcohol's
sedative effects were studied using loss-of-righting-reflex (LORR) and voluntary
ethanol intake was assessed using a two-bottle choice (TBC) procedure. Results showed that mice depleted of CD81 exhibited an
anxiolytic-like response in the EPM and OF tests with no effect on locomotor activity. In addition, genetic reduction of CD81 in the Nacc increased mice' sensitivity to alcohol's
sedative effects in the LORR test, although plasma alcohol concentrations were unaffected. Interestingly, CD81 loss-of-function-induced anxiolysis was accompanied by a significant decrease in
ethanol, but not
saccharin nor
quinine, intake in the TBC procedure. Finally, and following CD81
mRNA quantification, Pearson's correlations showed a significant positive relationship between accumbal CD81
mRNA with anxiety and
ethanol-related behaviors. Our data indicate that CD81 is implicated in the pathogenesis of anxiety and
alcoholism. Indeed the targeted disruption of CD81, with the resultant decrease in CD81
mRNA in the Nacc, converted
ethanol-"preferring" mice into
ethanol "non-preferring" mice. Collectively, these findings demonstrate that future CD81-targeted
pharmacotherapies may be beneficial for the treatment of anxiety and
alcoholism.