Cocaine Self-Administration Influences Central Nervous System Immune Responses in Male HIV-1 Transgenic Rats.

Cocaine use increases the neurotoxic severity of human immunodeficiency virus-1 ( HIV-1 ) infection and the development of HIV-associated neurocognitive disorders ( HAND ). Among the studied cellular mechanisms promoting neurotoxicity in HIV-1 and cocaine use, central nervous system ( CNS ) immunity, such as neuroimmune signaling and reduced antiviral activity, are risk determinants; however, concrete evidence remains elusive. In the present study, we tested the hypothesis that cocaine self-administration by transgenic HIV-1 ( HIV-1 Tg ) rats promotes CNS inflammation. To test this hypothesis, we measured cytokine, chemokine, and growth factor protein levels in the frontal cortex (f CTX ) and caudal striatum (c STR ). Our results demonstrated that cocaine self-administration significantly increased fCTX inflammation in HIV-1 Tg rats, but not in the cSTR. Accordingly, we postulate that cocaine synergizes with HIV-1 proteins to increase neuroinflammation in a region-selective manner, including the fCTX. Given the fCTX role in cognition, this interaction may contribute to the hyperimmunity and reduced antiviral activity associated with cocaine-mediated enhancement of HAND.