Effects of amphetamine exposure in adolescence or young adulthood on inhibitory control in adult male and female rats.
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.
Neuroscience Program, University of Illinois, Urbana-Champaign, USA.
Lindsey R
LR
Hammerslag
Department of Psychology, University of Illinois, Urbana-Champaign, USA.
Alex J
AJ
Waldman
Neuroscience Program, University of Illinois, Urbana-Champaign, USA; Department of Psychology, University of Illinois, Urbana-Champaign, USA. Electronic address: jgulley@illinois.edu.
Joshua M
JM
Gulley
D000367:Age Factors; D000661:Amphetamine / Q000009:adverse effects / Q000494:pharmacology*; D000818:Animals; D001143:Arousal / Q000187:drug effects / Q000502:physiology; D000697:Central Nervous System Stimulants / Q000009:adverse effects / Q000494:pharmacology*; D016291:Dizocilpine Maleate / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D005260:Female; D007175:Impulsive Behavior; D007266:Inhibition, Psychological; D007858:Learning / Q000187:drug effects / Q000502:physiology; D008297:Male; D009043:Motor Activity / Q000187:drug effects / Q000502:physiology; D017397:Prefrontal Cortex / Q000187:drug effects* / Q000254:growth & development / Q000503:physiopathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012737:Sex Factors; D013647:Task Performance and Analysis
D000697:Central Nervous System Stimulants; D018691:Excitatory Amino Acid Antagonists; D016291:Dizocilpine Maleate; D000661:Amphetamine
Adolescence; Amphetamine; Glutamate; Impulsivity; Rat; Sex differences