Effects of chronic delta‐9‐tetrahydrocannabinol (THC) administration on the acquisition and performance of response sequences during simian immunodeficiency virus (SIV) infection in rhesus macaques

Abstract

Although THC is used to treat wasting associated with acquired immune deficiency syndrome (AIDS), it may also contribute to the progression of human immunodeficiency virus (HIV) infection and disrupt complex behavioral processes such as learning. To investigate these possibilities, four groups of young adult male rhesus macaques were trained to respond under a multiple schedule with repeated acquisition and performance components and administered vehicle or THC (0.32 mg/kg, i.m., twice daily) in the presence or absence of SIV infection (SIVmac251; 100 TCID50/ml, i.v.). Prior to chronic THC administration and SIV inoculation, THC (0.032‐0.32 mg/kg) produced dose‐dependent rate‐decreasing effects in the acquisition and performance components in all groups, while producing only small error‐increasing effects. After 28 days of chronic injections, subjects developed tolerance to the behavioral disruptions produced by the chronic THC dose in both components of the multiple schedule. Tolerance was also maintained during the initial 6‐mo of SIV infection in the THC groups (+THC/‐SIV, +THC/+SIV). Together, these data indicate tolerance develops to the disruptive effects of THC on the acquisition and performance of response sequences during chronic administration and that this tolerance is not affected by the early stages of SIV infection. Supported by DA 019625 and DA 020419.