Title:Estrous Cycle and HIV-1 Tat Protein Influence Cocaine-Conditioned Place Preference and Induced Locomotion of Female Mice
Volume: 12
Issue: 6
Author(s): Jason J. Paris, Jason Fenwick and Jay P. McLaughlin
Affiliation:
Keywords:
Cocaine, conditioned place preference, estrous cycle, human immunodeficiency virus, NeuroAIDS, sensitization,
steroid hormones, trans-activator of transcription.
Abstract: The HIV-1 trans-activator of transcription (Tat) protein, interacts with psychostimulants
to potentiate cocaine-reward in rodents. Sex steroids may protect against Tat-induced deficits.
Female GT-tg transgenic mice conditionally-expressed Tat protein targeted to brain via a
doxycycline-dependent, GFAP-linked promoter. Mice were tested for cocaine-conditioned place
preference (CPP) and cocaine-induced locomotion when in the proestrous (high-hormone) or
diestrous (low-hormone) phases of their estrous cycle. Cocaine-CPP was potentiated by Tat
induction via 50, 100, or 125 (but not 25) mg/kg doxycycline daily treatment for 7 days. Diestrous
mice exposed to Tat protein demonstrated significantly greater cocaine-CPP than did proestrous
mice. Tat induction interacted with estrous cycle to decrease acute cocaine-induced locomotion
among Tat-induced diestrous mice, but not their uninduced or proestrous counterparts, and
attenuated cocaine-sensitization. In a cocaine-challenge, previously cocaine-sensitized mice
demonstrated greater cocaine-locomotion over cocaine-naive counterparts and Tat-induction
attenuated locomotion. Altogether, data demonstrate Tat and circulating sex steroid influences over cocaine-reward and
psychostimulation.