Effects of conditional central expression of HIV-1 tat protein to potentiate cocaine-mediated psychostimulation and reward among male mice.
As a major neuropathogenic factor associated with human immunodeficiency virus (HIV) infection, HIV-1 Tat protein is known to synergize with psychostimulant drugs of abuse to cause neurotoxicity and exacerbate the progression of central nervous system pathology. However, the functional consequences of the interaction between HIV-1 Tat and abused drugs on behavior are little known. We tested the hypothesis that HIV-1 Tat expression in brain would modulate the psychostimulant effects of cocaine. Using the GT-tg bigenic mouse model, where brain-selective Tat expression is induced by activation of a doxycycline (Dox) promotor, we tested the effects of Tat on cocaine (10 mg/kg, s.c.) induced locomotion and conditioned place preference (CPP). Compared with uninduced littermates or C57BL/6J controls, cocaine-induced hyperlocomotion was sustained for a significantly longer duration among Tat-induced mice. Moreover, although all groups displayed similar saline-CPP, Tat-induced GT-tg mice demonstrated a three-fold increase in cocaine-CPP over the response of either uninduced littermates or Dox-treated C57BL/6J control mice. Induction of Tat also increased the magnitude of a previously established cocaine-CPP after an additional cycle of cocaine place-conditioning. Despite Tat-induced potentiation, extinction of place preference occurred within 21 days, commensurate with cocaine-extinction among saline-treated littermates and C57BL/6J controls. Re-exposure to cocaine produced reinstatement of an equivalent place preference in Tat-induced GT-tg or C57BL/6J mice; however, induction of Tat protein after the extinction of CPP also produced reinstatement without additional exposure to cocaine. Together, these data suggest that central HIV-1 Tat expression can potentiate the psychostimulant behavioral effects of cocaine in mice.
Department of Pharmacology and Neuroscience, Torrey Pines Institute for Molecular Studies, Port Saint Lucie, FL, USA.
Jason J
JJ
Paris
1] Department of Psychology, Northeastern University, Boston, MA, USA [2] Department of Psychology, Simmons College, Boston, MA, USA.
Amanda N
AN
Carey
Department of Psychology, Northeastern University, Boston, MA, USA.
Christopher F
CF
Shay
1] Department of Pharmacology and Neuroscience, Torrey Pines Institute for Molecular Studies, Port Saint Lucie, FL, USA [2] Department of Psychology, Northeastern University, Boston, MA, USA.
Stacey M
SM
Gomes
Department of Cell Biology and Anatomy, University of North Texas Health Science Center, Fort Worth, TX, USA.
Johnny J
JJ
He
1] Department of Pharmacology and Neuroscience, Torrey Pines Institute for Molecular Studies, Port Saint Lucie, FL, USA [2] Department of Psychology, Northeastern University, Boston, MA, USA.
Jay P
JP
McLaughlin
D000818:Animals; D000697:Central Nervous System Stimulants / Q000494:pharmacology*; D003042:Cocaine / Q000494:pharmacology*; D003213:Conditioning, Psychological / Q000187:drug effects / Q000502:physiology*; D004357:Drug Synergism; D005786:Gene Expression Regulation / Q000187:drug effects*; D015497:HIV-1; D006801:Humans; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D012201:Reward; D054322:tat Gene Products, Human Immunodeficiency Virus / Q000096:biosynthesis / Q000235:genetics* / Q000502:physiology*
D000697:Central Nervous System Stimulants; D054322:tat Gene Products, Human Immunodeficiency Virus; D003042:Cocaine