Pilot Award Recipient: Alexander Zestos, PhD

Background: Although the relationship between HIV and intravenous drug use is well-established as drugs impact the likelihood of acquiring (or exacerbating) viral infection, HIV may also impact use and abuse of illicit drugs as a function of neurocognitive deficits associated with this infection. This possible association stems from work demonstrating that escalated and dysregulated drug use is a function of neuroplasticity that affects cognitive function normally inhibiting drug intake. While a number of drugs are used intravenously in people living with HIV, one group of drugs receiving increasing attention are the opiates as opiate users nearly tripled from 2009-2016. Heroin specifically is of major concern given its high vulnerability to abuse (over 60% of past year’s heroin users display substance use disorder) and the escalation of heroin and other opioid fatal overdoses over the past 10 years. To address the effects of HIV-associated cognitive impairments on drug intake, the present proposal will address the intravenous self-administration of heroin in the EcoHIV-infected mouse model. Specific Aim 1: Assess patterns of intravenous self-administration of heroin in EcoHIV-infected mice. Specific Aim 2: Assess potential neurochemical changes and neuroanatomical damage evident in EcoHIV-infected mice that may mediate the neurocognitive deficits facilitating patterns of dysregulated drug use. The contribution of cognitive compromise in people living with HIV to initiate drug use is not known. Recent work in the EcoHIV-infected mouse has revealed a number of cognitive deficits in several behavioral tasks that parallel the deficits seen in cognitive function in individuals with HIV. Aim 1 will assess the vulnerability of this specific animal model to the acquisition and escalation of heroin intravenous self-administration (a model of drug reward and abuse potential reflective of neurocognitive impairment). Several procedures used in assaying response effort (willingness to work for the drug), extinction of responding (the inability of response inhibition) and response reinstatement (or relapse; the inability to inhibit drug responding in the presence of the drug, drug-associated cues or stress) will be measured. Aim 2 will assess potential neurochemical changes and neuroanatomical damage evident in EcoHIV-infected mice that may mediate the neurocognitive deficits facilitating patterns of dysregulated drug use, and sex differences will be examined. This work should provide evidence in a well-characterized animal model of HIV if the substance use and abuse patterns reflective of cognitive deficits are present. Such data would implicate the fact that neurocognitive changes seen in individuals with HIV may exacerbate and dysregulate drug use which, in turn, may worsen the progression of HIV. Understanding the relationship between HIV-associated neurocognitive deficits and dysregulated drug use may provide insight into their interaction and basis for prevention and treatment of substance use disorders in people living with HIV.