Sex differences in cognitive function following methamphetamine exposure in young mice.




Vann, Philip
Davis, Delaney
Wong, Jessica
Shetty, Ritu
Forster, Michael
Sumien, Nathalie


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Prescription stimulant misuse among youth has dramatically increased in the United States, with amphetamine compounds gaining popularity in college students. Overall, 20% of college students have reported stimulant misuse to improve their academic performance. There are reported sex differences in psychostimulant use: males use it more frequently but females use it at earlier ages and are more vulnerable to reinforcing effects and dependence. The purpose of this pilot study was to determine if exposure to a prototypical psychostimulant, methamphetamine (meth), would lead to cognitive impairments in young male and female mice. Groups of 4 month old C57BL/6J mice received either saline or methamphetamine (1 mg/kg; i.p.) twice a day for 4 weeks. Two weeks following the last injection, animals were tested for cognitive function using 3 different tests: Morris water maze, active avoidance and fear conditioning. Spatial learning seemed impaired in males but not females, after meth exposure. In active avoidance, female performance was impaired by meth in the learning phase but their cognitive flexibility was not affected, while it was the opposite for males. Fear conditioning response was reduced by meth exposure only in the females. These preliminary results suggest sex-dependent methamphetamine-induced impairments in cognitive function of young mice. Meth exposure impaired spatial memory and cognitive flexibility in males and impaired associative learning in females. While our Ns are too low to obtain significance, these outcomes suggest that further studies are needed and support the use of both sexes in rodent preclinical research of substance abuse.