TY - JOUR PY - 2022// TI - Sex differences in neurobehavioral consequences of methamphetamine exposure in adult mice JO - Psychopharmacology A1 - Davis, Delaney L. A1 - Metzger, Daniel B. A1 - Vann, Philip H. A1 - Wong, Jessica M. A1 - Subasinghe, Kumudu H. A1 - Garlotte, Isabelle K. A1 - Phillips, Nicole R. A1 - Shetty, Ritu A. A1 - Forster, Michael J. A1 - Sumien, Nathalie SP - ePub EP - ePub VL - ePub IS - ePub N2 - RATIONALE: Recreational and medical use of stimulants is increasing, and their use may increase susceptibility to aging and promote neurobehavioral impairments. The long-term consequences of these psychostimulants and how they interact with age have not been fully studied.

OBJECTIVES: Our study investigated whether chronic exposure to the prototypical psychostimulant, methamphetamine (METH), at doses designed to emulate human therapeutic dosing, would confer a pro-oxidizing redox shift promoting long-lasting neurobehavioral impairments.

METHODS: Groups of 4-month-old male and female C57BL/6 J mice were administered non-contingent intraperitoneal injections of either saline or METH (1.4 mg/kg) twice a day for 4 weeks. Mice were randomly assigned to one experimental group: (i) short-term cognitive assessments (at 5 months), (ii) long-term cognitive assessments (at 9.5 months), and (ii) longitudinal motor assessments (at 5, 7, and 9 months). Brain regions were assessed for oxidative stress and markers of neurotoxicity after behavior testing.

RESULTS: Chronic METH exposure induced short-term effects on associative memory, gait speed, dopamine (DA) signaling, astrogliosis in females, and spatial learning and memory, balance, DA signaling, and excitotoxicity in males. There were no long-term effects of chronic METH on cognition; however, it decreased markers of excitotoxicity in the striatum and exacerbated age-associated motor impairments in males.

CONCLUSION: In conclusion, cognitive and motor functions were differentially and sex-dependently affected by METH exposure, and oxidative stress did not seem to play a role in the observed behavioral outcomes. Future studies are necessary to continue exploring the long-term neurobehavioral consequences of drug use in both sexes and the relationship between aging and drugs.

Language: en

LA - en SN - 0033-3158 UR - http://dx.doi.org/10.1007/s00213-022-06122-8 ID - ref1 ER -