Behavioral and Molecular Evidence for a Feedback Interaction Between Morphine and HIV-1 Viral Proteins

Abstract

Morphine use and addiction is common among HIV infected individuals. There is an abundance of research supporting the effects of morphine and other mu opioid receptor (MOR) ligands, on the function of HIV-1 viral proteins and progression of HIV-1 viral infection to AIDS. On the other hand, there is much less research that investigates the possible effects of the persistent presence of HIV-1 viral proteins on the expression of the MOR and the analgesic and rewarding effects of MOR ligands such as morphine. While researchers have made a great deal of progress in the past several years, the overall investigation of the interaction between opiates such as morphine and HIV-1 viral proteins is largely unilateral. It has become widely accepted that drugs of abuse interact with HIV-1 viral proteins, but the mechanisms by which this takes place are only recently being discovered. Molecular and behavioral research suggests a feedback interaction between morphine and HIV-1 viral proteins. This interaction is mediated largely by the MOR as well as interplay between MOR ligands and cytokines, chemokines and their receptors. Some of the mechanisms underlying the feedback interaction between morphine and HIV-1 viral proteins has been demonstrated using cell culture and the recently engineered HIV-1 transgenic (HIV-1Tg) rat models.

NeuroHIV and Use of Addictive Substances

“…In summary, the presence of HIV-1 viral proteins leads to a decrease in DA receptors (Liu et al, 2009) and may explain the behavioral evidence that indicates that HIV-1Tg rats are more prone to addiction (Chang & Connaghan, 2012;.…”

“…Statistical and bioinformatics analyses of each brain region between the two strains revealed that immune response-related pathways are altered in the HIV-1Tg rat, with brain region differences, suggesting that the persistent presence of HIV viral proteins causes inflammation in the brain of the HIV-1Tg rat (Li et al, 2013). In addition, analysis of serum cytokine levels revealed that, while LPS induces a significant increase in tumor necrosis factor-alpha (TNF-α) and interleukin-1 beta in both F344 and HIV-1Tg rats, the increase in these cytokines was significantly greater in the HIV-1Tg rats (Chang & Connaghan, 2012;Rao et al, 2011).…”

“…Chang and Connaghan (2012) proposed the possibility that a positive feedback interaction exists between opioid receptor-dependent pathways and HIV progression and that this interaction is, at least partly, moderated by HIV-induced neuroinflammation (Chang & Connaghan, 2012).…”

“…Neuroinflammation also leads to alterations in neurotransmitterdependent pathways associated with addictive behavior (Chang & Connaghan, 2012;Homji et al, 2012;Li et al, 2013;Trigo et al, 2010). Neuroinflammation can cause neuronal damage leading to deregulation of the dopaminergic system.…”

“…Morphine increases the expression of chemokine receptors (Mahajan, Schwartz, Shanahan, Chawda, & Nair, 2002;Rogers & Peterson, 2003), which are major coreceptors for the HIV-1 virus (Horuk et al, 1997), thereby increasing the susceptibility of HIV-infected individuals to opportunistic infections. Chang and Connaghan (2012) proposed the possibility that a positive feedback interaction exists between the MOR and HIV progression, and that this interaction is, at least partly, moderated by HIVinduced neuroinflammation (Chang & Connaghan, 2012). Using tail-flick latency as a measure of the antinociceptive effects of morphine, Vigorito and Chang (2006) demonstrated that HIV-1Tg rats exhibit an increased sensitivity to morphine's antinociceptive properties.…”