Background: Methamphetamine abuse and human immunodeficiency virus (HIV) are
common comorbidities. HIV-associated proteins, such as the regulatory protein TAT, may contribute
to brain reward dysfunction, inducing an altered sensitivity to methamphetamine reward and/or
withdrawal in this population.
Objective: These studies examined the combined effects of TAT protein expression and, chronic and
binge methamphetamine regimens on brain reward function.
Methods: Transgenic mice with inducible brain expression of the TAT protein were exposed to either
saline, a chronic, or a binge methamphetamine regimen. TAT expression was induced via
doxycycline treatment during the last week of methamphetamine exposure. Brain reward function
was assessed daily throughout the regimens, using the intracranial self-stimulation procedure, and
after a subsequent acute methamphetamine challenge.
Results: Both methamphetamine regimens induced withdrawal-related decreases in reward function.
TAT expression substantially, but not significantly increased the withdrawal associated with exposure
to the binge regimen compared to the chronic regimen, but did not alter the response to acute
methamphetamine challenge. TAT expression also led to persistent changes in adenosine 2B receptor
expression in the caudate putamen, regardless of methamphetamine exposure. These results suggest
that TAT expression may differentially affect brain reward function, dependent on the pattern
of methamphetamine exposure.
Conclusion: The subtle effects observed in these studies highlight that longer-term TAT expression,
or its induction at earlier stages of methamphetamine exposure, may be more consequential at inducing
behavioral and neurochemical effects.