title: Prepulse inhibition in HIV-1 gp120 transgenic mice after withdrawal from chronic methamphetamine.
abstract: HIV infection is frequently comorbid with methamphetamine (METH) dependence. Both factors are associated with impairment in inhibitory function that continues even after abstinence from the drug. Deficits in prepulse inhibition (PPI), a measure of sensorimotor gating, are induced by acute stimulant administration, but the combined effect of HIV and chronic METH exposure on PPI is not well characterized. We quantified baseline acoustic startle and PPI in mice expressing the HIV-1 gp120 envelope protein (gp120tg) and in wild-type (WT) littermates; thereafter, we administered a chronic regimen of METH or vehicle and tested startle and PPI after 7 days of drug withdrawal. We hypothesized that METH-treated gp120tg mice would exhibit PPI deficits compared with vehicle-treated WT or gp120tg animals. Before METH administration, drug-naive female gp120tg mice exhibited decreased PPI compared with female WT mice, whereas male gp120tg mice exhibited increased startle compared with other groups. After drug withdrawal, no consistent genotype effect was observed, but METH-treated mice exhibited increased PPI compared with vehicle, in contrast to previous reports of acute METH-induced PPI deficits. In summary, PPI impairment in HIV could depend on factors such as sex, whereas changes in PPI following METH withdrawal may depend on the quantity and duration of drug exposure.
authors.affiliation: aDepartment of Psychiatry, University of California, San Diego bResearch Service, VA San Diego Healthcare System cCenter of Excellence for Stress and Mental Health, (CESAMH), Veteran's Administration, San Diego, California, USA.
authors.forename: Brook L
authors.initials: BL
authors.lastname: Henry
authors.forename: Mark A
authors.initials: MA
authors.lastname: Geyer
authors.forename: Mahalah R
authors.initials: MR
authors.lastname: Buell
authors.forename: William
authors.initials: W
authors.lastname: Perry
authors.forename: Jared W
authors.initials: JW
authors.lastname: Young
authors.forename: Arpi
authors.initials: A
authors.lastname: Minassian
mesh_terms: D000161:Acoustic Stimulation; D000704:Analysis of Variance; D000818:Animals; D000697:Central Nervous System Stimulants / Q000009:adverse effects*; D004334:Drug Administration Schedule; D005260:Female; D015699:HIV Envelope Protein gp120 / Q000235:genetics; D006801:Humans; D007794:Lameness, Animal / Q000209:etiology* / Q000821:virology; D008297:Male; D008694:Methamphetamine / Q000009:adverse effects*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009433:Neural Inhibition / Q000187:drug effects / Q000502:physiology*; D013216:Reflex, Startle / Q000187:drug effects / Q000502:physiology*; D012737:Sex Factors; D013375:Substance Withdrawal Syndrome / Q000150:complications*; D013997:Time Factors
chemical_list: D000697:Central Nervous System Stimulants; D015699:HIV Envelope Protein gp120; D008694:Methamphetamine