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Publication Abstract Display
Type: Poster
Title: Expression of HIV gp120 protein increases sensitivity to the rewarding properties of methamphetamine in mice.
Authors: Semenova S, Kesby JP, Hubbard DT, Markou A
Date: 05-29-2012
Abstract:Methamphetamine (METH) abuse and Human Immunodeficiency Virus (HIV) infection induce neuropathological changes in corticolimbic brain areas involved in reward and cognitive function. Little is known about the combined effects of METH and HIV infection on cognitive and reward processes. The HIV/gp120 protein induces neurodegeneration in mice similar to HIV-induced pathology in humans. We investigated the effects of gp120 expression on associative learning, preference for METH and non-drug reinforcers (saccharine and quinine), and sensitivity to the conditioned rewarding properties of METH in transgenic mice expressing HIV/gp120 protein (gp120-tg). The gp120-tg mice learned the operant response for food at the same rate as non-tg mice indicating no deficits in associative learning and unimpaired reward and motivational function for a natural reinforcer. In the two-bottle choice procedure with restricted access to drinking solutions, gp120-tg mice exhibited greater preference towards METH and saccharin compared to non-tg mice; while preference for quinine was similar between genotypes. Under conditions with unrestricted access to METH self-administration, all mice, independent of genotype and sex, decreased preference for METH indicative of METH-induced aversion. However, male gp120-tg mice decreased preference for METH at lower concentrations than non-tg male mice indicating higher sensitivity to the aversive effects of METH. The gp120-tg mice developed METH-induced conditioned place preference at lower METH doses compared to non-tg mice indicating higher sensitivity to the conditioned rewarding effects of METH. There were no differences in METH pharmacokinetics between genotypes. These results indicate that gp120 expression is associated with increased preference for METH and highly palatable non-drug reinforcer (saccharine), and increased sensitivity to METH-induced conditioned reward. Nevertheless, the sensitivity to the rewarding and motivational properties of a natural reinforcer was similar between genotypes. These data suggest that HIV positive individuals may have increased sensitivity to METH leading to high abuse potential of METH in this population.

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