title: Behavioral effects of chronic methamphetamine treatment in HIV-1 gp120 transgenic mice.
abstract: 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.
authors.affiliation: University of California San Diego, Department of Psychiatry, La Jolla, CA, United States.
authors.forename: Brook L
authors.initials: BL
authors.lastname: Henry
authors.affiliation: University of California San Diego, Department of Psychiatry, La Jolla, CA, United States; VA San Diego Healthcare System, San Diego, CA, United States.
authors.forename: Mark A
authors.initials: MA
authors.lastname: Geyer
authors.affiliation: University of California San Diego, Department of Psychiatry, La Jolla, CA, United States.
authors.forename: Mahalah
authors.initials: M
authors.lastname: Buell
authors.affiliation: University of California San Diego, Department of Psychiatry, La Jolla, CA, United States.
authors.forename: William
authors.initials: W
authors.lastname: Perry
authors.affiliation: University of California San Diego, Department of Psychiatry, La Jolla, CA, United States.
authors.forename: Jared W
authors.initials: JW
authors.lastname: Young
authors.affiliation: University of California San Diego, Department of Psychiatry, La Jolla, CA, United States; Center for Excellence in Substance Abuse and Mental Health (CESAMH), Veteran's Administration, San Diego, CA, United States. Electronic address: aminassian@mail.ucsd.edu.
authors.forename: Arpi
authors.initials: A
authors.lastname: Minassian
mesh_terms: D000375:Aging / Q000523:psychology; D019969:Amphetamine-Related Disorders / Q000523:psychology; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D001831:Body Temperature / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D000697:Central Nervous System Stimulants / Q000494:pharmacology*; D003624:Darkness; D004305:Dose-Response Relationship, Drug; D005106:Exploratory Behavior / Q000187:drug effects; D005260:Female; D015699:HIV Envelope Protein gp120 / Q000235:genetics*; D015658:HIV Infections / Q000523:psychology; D008027:Light; D008297:Male; D008694:Methamphetamine / Q000494:pharmacology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009043:Motor Activity / Q000187:drug effects / Q000502:physiology; D012727:Sex Characteristics
chemical_list: D000697:Central Nervous System Stimulants; D015699:HIV Envelope Protein gp120; D008694:Methamphetamine