HIV-1 Proteins Influence Novelty-Seeking Behavior and Alter Region-Specific Transcriptional Responses to Chronic Nicotine Treatment in HIV-1Tg Rats.
BACKGROUND
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, nucleus accumbens, and ventral tegmental area 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 prefrontal cortex and Drd5 and Gabra6 in the ventral tegmental area was significantly upregulated, whereas that of Drd5 in the nucleus accumbens 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.


CONCLUSIONS
HIV-1 viral proteins and chronic nicotine treatment impact the expression of genes involved in novelty-seeking behavior and addiction in three brain regions of the HIV-1 transgenic rat. These findings implicate that HIV-1 proteins may be involved in novelty-seeking behavior and in modulating the expression of genes related to drug addiction and novelty seeking.
State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Zhejiang University School of Medicine, Hangzhou, China.|Research Center for Air Pollution and Health, Zhejiang University, Hangzhou, China.|Institute of NeuroImmune Pharmacology, Seton Hall University, South Orange, NJ.
Zhongli
Z
Yang
Department of Psychiatry and Neurobehavioral Sciences, University of Virginia, Charlottesville, VA.
Tanseli
T
Nesil
Department of Psychiatry and Neurobehavioral Sciences, University of Virginia, Charlottesville, VA.
Taylor
T
Wingo
Institute of NeuroImmune Pharmacology, Seton Hall University, South Orange, NJ.|Department of Biology, Seton Hall University, South Orange, NJ.
Sulie L
SL
Chang
State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Zhejiang University School of Medicine, Hangzhou, China.|Research Center for Air Pollution and Health, Zhejiang University, Hangzhou, China.|Department of Psychiatry and Neurobehavioral Sciences, University of Virginia, Charlottesville, VA.
Ming D
MD
Li
D000818:Animals; D001923:Brain Chemistry / Q000187:drug effects / Q000235:genetics / Q000502:physiology; D005106:Exploratory Behavior; D015497:HIV-1; D009538:Nicotine / Q000378:metabolism / Q000494:pharmacology; D051381:Rats; D055647:Rats, Transgenic; D014764:Viral Proteins
D014764:Viral Proteins; D009538:Nicotine