Rhesus Macaque Model of Chronic Opiate Dependence and Neuro-AIDS: Longitudinal Assessment of Auditory Brainstem Responses and Visual Evoked Potentials

Abstract

Our work characterizes the effects of opiate (morphine) dependence on auditory brainstem and visual evoked responses in a rhesus macaque model of neuro-AIDS utilizing a chronic continuous drug delivery paradigm. The goal of this study was to clarify whether morphine is protective, or if it exacerbates simian immunodeficiency virus (SIV) related systemic and neurological disease. Our model employs a macrophage tropic CD4/CCR5 co-receptor virus, SIVmac239 (R71/E17), which crosses the blood brain barrier shortly after inoculation and closely mimics the natural disease course of human immunodeficiency virus (HIV) infection. The cohort was divided into 3 groups: morphine only, SIV only, and SIV + morphine. Evoked potential (EP) abnormalities in sub-clinically infected macaques were evident as early as eight weeks post-inoculation. Prolongations in EP latencies were observed in SIV-infected macaques across all modalities. Animals with the highest CSF viral loads and clinical disease showed more abnormalities than those with sub-clinical disease, confirming our previous work (Raymond et al, 1998, 1999, 2000). Although some differences were observed in auditory and visual evoked potentials in morphine treated compared to untreated SIV-infected animals, the effects were relatively small and not consistent across evoked potential type. However, morphine treated animals with subclinical disease had a clear tendency toward higher virus loads in peripheral and CNS tissues (Marcario et al., 2008) suggesting that if had been possible to follow all animals to end-stage disease, a clearer pattern of evoked potential abnormality might have emerged.

Opiate use inhibits TLR9 signaling pathway in vivo: possible role in pathogenesis of HIV-1 infection

“…Consistent with previous studies 7,39,40 , our results, which are based on a population study, showed that opiate use was associated with higher HIV-1 viral load and lower CD4 + T cell count among HIV-1-infected patients, providing compelling in vivo evidence to support the opinion that abuse of opiates acted as a cofactor in promoting HIV infection and disease progression. One of the possibilities for opiate action is that opiate can suppress the functional activity of innate immunity and consequently is detrimental to the host’s ability to eradicate pathogens 10 .…”

Effects of Morphine on Behavioral Task Performance in SIV-Infected Rhesus Macaques

“…Previous studies from our group have shown that morphine potentiates neuropathognesis in macaques infected with SIV mac R71/17E (Marcario et al, 2008; Bokhari et al, 2011). Such morphine mediated viral pathogenesis also resulted in alterations in brain stem responses and visual evoked potentials (Raymond et al, 1998; Cheney et al, 2008; Riazi et al, 2009). In the current study we assessed behavioral task performance using three groups of Indian rhesus macaques chronically treated with morphine to establish dependence and then infected with SIVmac R71/17E.…”

“…Morphine injection and viral infection regimens used in the current study have been reported in our previous work (Marcario et al, 2008; Riazi et al, 2009). Our morphine regimen was based on a protocol introduced by (Seevers MH, 1963) and used by others (Aceto et al, 1977; Aceto et al, 1981) for establishing dependence.…”

Time and time again: Temporal processing demands implicate perceptual and gating deficits in the HIV-1 transgenic rat

“…Simian and feline immunodeficiency virus models have also demonstrated alterations in evoked potentials (Phipps et al 2000;Prospero-Garcia et al 1999;Raymond et al 1998;Riazi et al 2009). …”