Methamphetamne (METH) is a mood-elevating, positively reinforcing drug of high abuse potential in humans. Continuous use of METH can lead to a number of adverse psychological, immunological, and permanent neurotoxicological effects. Species sensitivity to the neurotoxicological effects vary, but are uniform in creating degeneration of serotonergic and dopaminergic nerve terminals of subcortical structures. Increasingly greater numbers of HIV-1 infected individuals are known METH abusers throughout the world. The synergistic effects of chronic METH abuse and HIV-1 infection are presently poorly understood. Both conditions have detrimental affects on the immune system and cause a progressive, subcortical mediated neurodegeneration. The cat is a well-suited animal model to study the synergistic effects of chronic METH abuse and HIV-1 infection. Cats exhibit a similar metabolism of and sensitivity to METH as humans. Moreover, a feline model of neuroAIDS is well-documented, resulting in a progressive, subcortical mediated neurodegeneration associated with immunodeficiency, behavioral disturbances, and neuronal loss after feline immunodeficiency virus (FIV) infection. Thus, the overall objective of this study is to evaluate the synergistic effects of FIV infection and chronic METH with acute """"""""binges"""""""" on immune function and viral interaction, neurobehavior and neurophysiology, and neurodegeneration. The overall hypothesis is that FIV and METH are synergistic in enhancing viral load, immunosuppression, altered behavior, and subsequent neurodegeneration.
Three specific aims will be studied: 1. Determine the pharmacokinetics patterns, immune function and viral load prior to and after METH administration to FIV infected cats over a 6 month period; 2. Determine the behavioral, physiologic, and neurochemical neurotoxicity of chronic METH administration in uninfected and FIV infected cats over a 2 year period; and 3. Determine the interaction of METH and FIV on glutamate uptake, release, and glutatmate metabolism as related to excitotoxic neuronal loss in the basal ganglia. The goal is to elucidate on the effects and mechanisms of METH and HIV-1 interaction.
| Gavrilin, Mikhail A; Mathes, Lawrence E; Podell, Michael (2002) Methamphetamine enhances cell-associated feline immunodeficiency virus replication in astrocytes. J Neurovirol 8:240-9 |
