Research reportBehavioral effects of chronic methamphetamine treatment in HIV-1 gp120 transgenic mice

Methamphetamine (METH) dependence is frequently comorbid with HIV infection. Both factors are independently characterized by inhibitory deficits, which may manifest as increased motor activity, inappropriate perseverative behavior, and elevated exploratory responses to novel stimuli, but the effect of combined METH exposure and HIV is not well understood. In this study, we administered a chronic escalation/binge regimen of METH or vehicle treatment to wildtype (WT) or transgenic (tg) mice expressing the HIV-1 gp120 envelope protein and quantified disinhibition during the 7 days following drug withdrawal. We hypothesized that gp120tg mice administered chronic METH would exhibit more pronounced inhibitory deficits compared to vehicle-treated WT or gp120tg animals. Our results showed that METH treatment alone increased novel object interaction while female METH-treated gp120tg mice exhibited the highest level of exploration (holepoking) compared to other female mice. Transgenic mice exhibited fewer rears relative to WT, slightly less locomotion, and also demonstrated a trend toward more perseverative motor patterns. In summary, both METH treatment and gp120 expression may modify inhibition, but such effects are selective and dependent upon variations in age and sex that could impact dopamine and frontostriatal function. These findings illustrate the need to improve our knowledge about the combined effects of HIV and substance use and facilitate improved treatment methods for comorbid disease and drug dependence.

► HIV infection and comorbid methamphetamine (METH) dependence impair inhibition. ► We studied open-field activity in chronic METH-treated HIV/gp120 transgenic mice. ► METH-treated gp120 female mice exhibited inhibitory deficits relative to control. ► METH and gp120 expression selectively impact inhibition based on age and sex. ► Additional studies are needed to elucidate the combined effects of HIV and METH.