Effects of amphetamine exposure in adolescence or young adulthood on inhibitory control in adult male and female rats

Lindsey R. Hammerslag, Alex J. Waldman, Joshua M. Gulley

Research output: Contribution to journalArticlepeer-review

24 Scopus citations


Heightened impulsivity is a feature of some psychiatric disorders, including addiction, that also have sex-specific patterns of expression. The relationship between addiction and impulsivity may be driven by drug-induced changes in behavior caused by long term adaptations in signaling within the medial prefrontal cortex (mPFC). Here, we used a response inhibition task that is sensitive to changes in mPFC function to examine the effects of sex and exposure to amphetamine (AMPH) on impulsive action and vigilance. We also examined drug-induced alterations in glutamatergic and dopaminergic signaling through challenge injections with the NMDA receptor antagonist MK-801 (dizocilpine) and AMPH. Male and female Sprague Dawley rats were injected (i.p.) with saline or 3. mg/kg AMPH every other day during adolescence (postnatal day (P) 27-45) or adulthood (P85-103). Starting on P125-135, rats were tested for their ability to lever press for a food reward during periods of signaled availability and withhold responding during a "premature response" phase. In experiment 1, rats received challenge injections (i.p.) of MK-801 and AMPH followed by tests of task performance and locomotor activity. In experiment 2, rats received intra-mPFC infusion of MK-801. We found that females had better inhibitory control and poorer vigilance than males and that AMPH exposure had both sex- and age-of-exposure dependent effects on impulsivity. Systemic drug challenges disrupted task performance, particularly in females, and increased impulsivity while intra-mPFC infusions had modest effects. AMPH exposure did not affect responses to drug challenges. Together, these results suggest that sex mediates both trait and drug-induced impulsivity.

Original languageEnglish
Pages (from-to)22-33
Number of pages12
JournalBehavioural Brain Research
StatePublished - Apr 15 2014

Bibliographical note

Funding Information:
This study was supported by a grant from the National Institute on Drug Abuse ( R01 DA029815 ). We thank John Weaver, Sapan Shah, Rakesh Marreddy and Olubankole Aladesuyi Arogundade for excellent technical assistance.


  • Adolescence
  • Amphetamine
  • Glutamate
  • Impulsivity
  • Rat
  • Sex differences

ASJC Scopus subject areas

  • Behavioral Neuroscience


Dive into the research topics of 'Effects of amphetamine exposure in adolescence or young adulthood on inhibitory control in adult male and female rats'. Together they form a unique fingerprint.

Cite this