Additionally, the nature of opiate exposure in the context of neuroHIV needs to be considered as it may induce different outcomes on neurotransmitter metabolism and gene expression. Specifically, the NAc shell demonstrates molecular and structural changes associated with intravenous heroin self-administration (Jacobs et al. 2005). Moreover, earlier studies have reported differential alterations in the turnover rates of various neurotransmitters for active versus passive morphine administration, including dopamine, serotonin, γ-aminobutyric acid (GABA), acetylcholine, aspartate, and glutamate during exposure to morphine (Smith et al. 1982, 1984). The disruptions were noticed specifically in brain regions involved in reinforcement processes, including the NAc, frontal cortex, and striatum, and encompassed increased dopamine and norepinephrine levels and turnover, which are central in opiate reward processes (Smith et al. 1982). Heroin abuse is known to downregulate dopaminergic activity in the NAc and may reflect a compensatory reduction in of dopamine biosynthesis in response to excessive dopaminergic stimulation resulting from chronic opiate exposure (Kish et al. 2001). Additionally, HIV is known to interfere with dopamine neurotransmission (Nath et al. 2000b; Gaskill et al. 2017) causing reductions in presynaptic dopamine terminals and dopamine transport in the striatum (Wang et al. 2004; Chang et al. 2008; Midde et al. 2012, 2015). The decline in dopamine function may exacerbate opioid abuse tendencies and drug-seeking behaviors as the rewarding effects of opioids are discounted by neuroHIV.