Age-dependent effects of repeated amphetamine exposure on working memory in rats

Luke K. Sherrill, Jessica J. Stanis, Joshua M. Gulley

Research output: Contribution to journalArticlepeer-review


Cognitive dysfunction is a hallmark of chronic psychostimulant misuse. Adolescents may have heightened risk of developing drug-induced deficits because their brains are already undergoing widespread changes in anatomy and function as a normal part of development. To address this hypothesis, we performed two sets of experiments where adolescent and young adult rats were pre-exposed to saline or amphetamine (1 or 3. mg/kg) and subsequently tested in a prefrontal cortex (PFC)-sensitive working memory task. A total of ten injections of AMPH or saline (in control rats) were given every other day over the course of 19 days. After rats reached adulthood (>90 days old), cognitive performance was assessed using operant-based delayed matching-to-position (DMTP) and delayed nonmatching-to-position (DNMTP) tasks. DNMTP was also assessed following challenges with amphetamine (0.3-1.25. mg/kg), and ketamine (5.0-10. mg/kg). In experiment one, we also measured the locomotor response following the first and tenth pre-exposure to amphetamine and after an amphetamine challenge given at the conclusion of operant testing. Compared to adult-exposed groups, adolescents were less sensitive to the psychomotor effects of amphetamine. However, they were more vulnerable to exposure-induced cognitive impairments. For example, adolescent-exposed rats displayed delay-dependent deficits in accuracy, increased sensitivity to proactive interference, and required more training to reach criterion. Drug challenges produced deficits in DNMTP performance, but these were not dependent on pre-exposure group. These studies demonstrate age of exposure-dependent effects of amphetamine on cognition in a PFC-sensitive task, suggesting a heightened sensitivity of adolescents to amphetamine-induced neuroplasticity.

Original languageEnglish (US)
Pages (from-to)84-94
Number of pages11
JournalBehavioural Brain Research
Issue number1
StatePublished - Apr 1 2013


  • Adolescence
  • Amphetamine
  • Matching-to-position
  • Sensitization
  • Working memory

ASJC Scopus subject areas

  • Behavioral Neuroscience


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