Abstract

Introduction:

Clinical studies suggest that HIV-1-infected patients are more likely to use or abuse addictive drugs than is the general population. We hypothesized that HIV-1 proteins impact novelty-seeking behavior and enhance the transcriptional response to nicotine in genes implicated in both novelty-seeking behavior and drug addiction.

Methods:

We assessed the effects of HIV-1 proteins on novelty-seeking behavior by comparing baseline activity differences of HIV-1Tg and F344 control rats in the open-field test. One day after behavioral testing, all rats began daily subcutaneous injections of either nicotine (0.4 mg/kg, base) or saline (the same for each rat) for 27 days. At the end of treatment, the prefrontal cortex (PFC), nucleus accumbens (NAc), and ventral tegmental area (VTA) were collected for RNA expression analysis of genes in the receptor families for dopamine, GABA, glutamate, and serotonin.

Results:

Significant strain difference was detected in the distance moved in the center, such that HIV-1Tg rats traveled greater distance in the center of the arena than did F344 rats. Quantitative RT-PCR analysis showed that mRNA from Drd3 and Grm2 in the PFC and Drd5 and Gabra6 in the VTA was significantly upregulated, whereas that of Drd5 in the NAc was downregulated in HIV-1Tg rats compared with F344 rats. Further, more addiction-related genes were significantly modulated by nicotine in each brain region in the HIV-1Tg rats than in the control animals.

Conclusions:

HIV-1 proteins may affect novelty-seeking behavior and modulate the expression of genes related to drug addiction and novelty-seeking behavior.

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