Title:HIV-1 Tat Protein Exposure Potentiates Ethanol Reward and Reinstates Extinguished Ethanol-Conditioned Place Preference
Volume: 12
Issue: 6
Author(s): Jay P. McLaughlin, Michelle L. Ganno, Shainnel O. Eans, Elisa Mizrachi and Jason J. Paris
Affiliation:
Keywords:
Alcohol abuse, conditioned place preference, ethanol, human immunodeficiency virus, NeuroAIDS, relapse,
reward, trans-activator of transcription.
Abstract: Exposure to HIV-1 trans-activator of transcription (Tat) protein potentiates the
psychostimulant effects of cocaine, but the functional consequences of the interaction between HIV-1
Tat and other abused drugs is poorly understood. We hypothesized that exposure to HIV-1 Tat would
potentiate the rewarding effects of ethanol. GT-tg transgenic mice, where Tat protein is conditionally
expressed in brain by a doxycycline-dependent GFAP-linked promoter, were used to test the effects
of Tat on ethanol-conditioned place preference (CPP). Compared to uninduced littermates or
doxycycline-treated C57BL/6J mice, Tat-induced GT-tg mice demonstrated a 3-fold increase in
ethanol-CPP. The potentiation of ethanol-CPP was dependent on the dose and duration of
doxycycline treatment used to express Tat protein. Moreover, induction of Tat protein after the
extinction of CPP produced reinstatement without additional exposure to ethanol. Together, these
data suggest that CNS exposure to HIV-1 Tat protein potentiates the rewarding effects of ethanol in mice.