Abstract
BACKGROUND: Novelty-seeking behavior is related to the reward system in the brain and can predict the potential for addiction. Alcohol use is prevalent in HIV-1-infected patients and adversely affects antiretroviral medication. The difference in vulnerability to alcohol addiction between HIV-1-infected and noninfected populations has not been fully investigated. This study was designed to determine whether HIV-1 proteins alter the effects of ethanol (EtOH) on novelty-seeking behavior using the HIV-1 transgenic (HIV-1Tg) rat as the study model and to examine the molecular mechanisms responsible for this behavior. METHODS: Both HIV-1Tg and F344 control rats were tested for baseline novelty-seeking behavior, then received either EtOH (1 g/kg) at a concentration of 20% v/v or saline treatment for 13 days, and then were retested for novelty seeking. Quantitative real-time polymerase chain reaction was conducted to examine the differences in expression of 65 genes implicated in novelty seeking and alcohol addiction between strains and treatment groups. RESULTS: The HIV-1 proteins significantly enhanced baseline novelty-seeking behaviors in both the hole-board and open-field tests. Chronic EtOH treatment significantly increased baseline novelty-seeking behavior in both strains, but the effects of EtOH appeared to be more robust and prominent in HIV-1Tg rats. Strain-specific patterns of altered gene expression were observed for dopaminergic, cholinergic, and glutamatergic signaling in the nucleus accumbens, suggesting the effects of HIV-1 proteins on the brain's reward system. Chronic EtOH treatment was shown to greatly modulate the effects of HIV-1 proteins in these neurotransmitter systems. CONCLUSIONS: Taken together, our findings indicate that HIV-1 proteins could modify novelty-seeking behavior at the gene expression level, and EtOH treatment may enhance this behavior in both strains but to a greater extent in HIV-1Tg rats.