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Publication Abstract Display
Type: Poster
Title: HIV-1 regulatory protein, TAT, decreases brain reward function and enhances methamphetamine reward.
Authors: Kesby J, Markou A, Semenova S
Date: 06-02-2015
Abstract:Psychostimulant abuse and depression are common comorbidities among humans with immunodeficiency virus (HIV) disease. The HIV regulatory protein TAT is one of multiple HIV-related proteins associated with HIV-induced neurotoxicity. TAT-induced neuropathology in corticolimbic brain areas may result in impaired reward function and, thus, contribute to depressive symptoms and psychostimulant abuse. Transgenic mice with doxycycline-induced TAT protein expression in the brain (TAT+) show neuropathology resembling brain abnormalities in humans with HIV disease. We evaluated brain reward function in response to TAT expression, nicotine and methamphetamine administration in TAT+ and TAT- (control) mice. Brain reward function was assessed using the intracranial self-stimulation procedure. Elevated current-intensity brain reward thresholds served as a measure of reward deficits, a core symptom of depression. Threshold lowering served as a measure of reward enhancement. After establishing stable baseline thresholds, TAT expression was induced by doxycycline administration for 7 days. Assessment of nicotine and methamphetamine dose-response functions in the intracranial self-stimulation procedure was initiated 2 weeks after the final doxycycline treatment. During doxycycline administration, thresholds were elevated by 20% in TAT+ mice compared with TAT- mice. After the termination of doxycycline treatment, thresholds decreased in all mice, regardless of TAT expression. However, thresholds of TAT+ mice remained significantly higher than those of TAT- mice for two weeks. Methamphetamine induced dose-dependent threshold lowering in all mice, with TAT+ mice showing greater methamphetamine-induced threshold lowering compared with TAT- mice. Nicotine tended to elevate reward thresholds with no significant differences between TAT+ and TAT-mice. These results indicate that TAT expression in mice leads to reward deficits and a greater sensitivity to methamphetamine-induced reward enhancement. Our findings suggest that the TAT protein may contribute to increased depressive-like symptoms and continued methamphetamine use in HIV-positive individuals.

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