HIV-1 protein Tat potentiation of methamphetamine-induced decreases in evoked overflow of dopamine in the striatum of the rat.
HIV-1 infection of the brain can lead to the development of clinical syndromes reminiscent of Parkinson's disease, suggesting that HIV infection may damage nigrostriatal dopamine (DA) neurons. Although the responsible mechanisms have not been well defined, neurotoxic viral proteins, such as Tat, released from infected cells may be involved. Drug abuse is a major risk factor for contracting HIV infection. Methamphetamine (METH), a psychostimulant with high abuse potential, may also be toxic to brain DA neurons. Thus, the combination of METH abuse and HIV infection may lead to substantial alterations in DA neuron functioning. The present experiments examined how Tat, alone and with METH, affects DA release in the striatum. Male rats were given an intrastriatal injection of Tat (25 micro g) or vehicle 24 h before treatment with saline or neurotoxic doses of METH. Seven days later microdialysis studies were carried out to measure potassium- and amphetamine-evoked overflow of DA from the striatum. The Tat treatment alone led to no change in potassium-evoked overflow of DA, a 20% decrease in amphetamine-evoked overflow of DA, and a 16% decrease in striatal DA content. The METH alone led to a 37-42% decrease in striatal DA overflow and content. The combined treatment with Tat and METH led to significantly greater 70-78% decreases in striatal DA overflow and content. These results indicate that Tat enhances METH-induced reductions in striatal DA release and content, possibly in a synergistic manner, and suggest that METH abusers infected with HIV may be at increased risk for basal ganglia dysfunction.
Cass
Wayne A
WA
Department of Anatomy and Neurobiology, MN-225 Chandler Medical Center, University of Kentucky College of Medicine, Lexington, KY 40536-0298, USA. wacass1@pop.uky.edu
Harned
Michael E
ME
Peters
Laura E
LE
Nath
Avindra
A
Maragos
William F
WF
D000818:Animals; D003342:Corpus Striatum / Q000187:drug effects* / Q000378:metabolism*; D004298:Dopamine / Q000378:metabolism*; D004357:Drug Synergism; D015696:Gene Products, tat / Q000494:pharmacology*; D008297:Male; D008694:Methamphetamine / Q000494:pharmacology*; D051381:Rats; D011916:Rats, Inbred F344; D054322:tat Gene Products, Human Immunodeficiency Virus
D015696:Gene Products, tat; D054322:tat Gene Products, Human Immunodeficiency Virus; C470431:tat peptide (1-72), Human immunodeficiency virus 1; D008694:Methamphetamine; D004298:Dopamine