Long-term effects of exposure to methamphetamine in adolescent rats

Drug Alcohol Depend. 2014 May 1:138:17-23. doi: 10.1016/j.drugalcdep.2014.02.021. Epub 2014 Feb 26.


Background: Flexible cognition is a set of processes mediated by the prefrontal cortex (PFC), an area of the brain that continues to develop during adolescence and into adulthood. Adult rodents exhibit impairments specific to reversal learning across various dosing regimens of methamphetamine (mAMPH). For adolescent rodents, ongoing PFC development can be assessed by discrimination reversal learning, a task dependent on frontostriatal integrity. The task may also index an increased vulnerability for mAMPH sampling in adulthood.

Methods: The purpose of the present study was to investigate the long-term effects of escalating, adolescent mAMPH exposure on reversal learning, a PFC-dependent task (Experiment 1) and the likelihood of later sampling of mAMPH in adulthood (Experiment 2).

Results: Unlike previous research in adult-treated rats, our results show more generalized learning impairments after adolescent mAMPH exposure to include both attenuated visual discrimination as well as reversal learning. Additionally, we found that rats pre-exposed to mAMPH during adolescence consumed significantly more drug in adulthood. Intake of mAMPH was positively correlated with this learning. Taken together, these findings show that even modest exposure to mAMPH during adolescence may induce general learning impairments in adulthood, and an enduring sensitivity to the effects of mAMPH.

Keywords: Adolescence; Cognitive flexibility; Frontal cortex; Plasticity; Reversal learning.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Aging* / drug effects
  • Animals
  • Choice Behavior / drug effects
  • Discrimination Learning / drug effects*
  • Learning Disabilities / chemically induced*
  • Male
  • Methamphetamine / administration & dosage
  • Methamphetamine / adverse effects*
  • Rats
  • Reversal Learning / drug effects*
  • Self Administration


  • Methamphetamine