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

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 exacerbat...

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Bibliographic Details
Published in:	Journal of neuroimmune pharmacology 2009-06, Vol.4 (2), p.260-275
Main Authors:	Riazi, Mariam, Marcario, Joanne K., Samson, Frank K., Kenjale, Himanshu, Adany, Istvan, Staggs, Vincent, Ledford, Emily, Marquis, Janet, Narayan, Opendra, Cheney, Paul D.
Format:	Article
Language:	eng
Subjects:	AIDS Dementia Complex - physiopathology AIDS Dementia Complex - virology Animals Biomedical and Life Sciences Biomedicine Brain - drug effects Brain - pathology Brain - virology Brain Diseases - physiopathology Brain Diseases - virology Cell Biology Disease Models, Animal Evoked Potentials, Auditory, Brain Stem - drug effects Evoked Potentials, Visual - drug effects Human immunodeficiency virus Immunology Macaca mulatta Monkeys & apes Morphine - pharmacology Narcotics Narcotics - pharmacology Neurosciences Opioid-Related Disorders - physiopathology Original Article Pharmacology/Toxicology Retrovirus Simian Acquired Immunodeficiency Syndrome - physiopathology Simian Acquired Immunodeficiency Syndrome - virology Simian immunodeficiency virus Viral Load Virology
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Summary:	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 coreceptor virus, SIV mac 239 (R71/E17), which crosses the blood-brain barrier shortly after inoculation and closely mimics the natural disease course of human immunodeficiency virus infection. The cohort was divided into three groups: morphine only, SIV only, and SIV + morphine. Evoked potential (EP) abnormalities in subclinically infected macaques were evident as early as 8 weeks postinoculation. Prolongations in EP latencies were observed in SIV-infected macaques across all modalities. Animals with the highest cerebrospinal fluid viral loads and clinical disease showed more abnormalities than those with subclinical disease, confirming our previous work (Raymond et al., J Neurovirol 4:512–520, 1998 ; J Neurovirol 5:217–231, 1999 ; AIDS Res Hum Retroviruses 16:1163–1173, 2000 ). Although some differences were observed in auditory and visual evoked potentials in morphine-treated compared to morphine-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 central nervous system tissues (Marcario et al., J Neuroimmune Pharmacol 3:12–25, 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.
ISSN:	1557-1890 1557-1904