Daily morphine administration increases impulsivity in rats responding under a 5-choice serial reaction time task

Br J Pharmacol. 2016 Apr;173(8):1350-62. doi: 10.1111/bph.13434. Epub 2016 Feb 26.

Abstract

Background and purpose: Repeated administration of a μ opioid receptor agonist can enhance some forms of impulsivity, such as delay discounting. However, it is unclear whether repeated administration alters motor impulsivity.

Experimental approach: We examined the effects of acute administration of morphine and amphetamine prior to and during daily morphine administration in rats responding under a five-choice serial reaction time task. Rats (n = 5) were trained to detect a brief flash of light presented randomly in one of five response holes; responding in the target hole delivered food, whereas responding in the wrong hole or responding prior to illumination of the target stimulus (premature response) initiated a timeout. Premature responding served as an index of motor impulsivity.

Key results: Administered acutely, morphine (0.1-10 mg·kg(-1) , i.p.) increased omissions and modestly, although not significantly, premature responding without affecting response accuracy; amphetamine (0.1-1.78 mg·kg(-1) , i.p.) increased premature responding without changing omissions or response accuracy. After 3 weeks of 10 mg·kg(-1) ·day(-1) morphine, tolerance developed to its effects on omissions whereas premature responding increased approximately fourfold, compared with baseline. Effects of amphetamine were not significantly affected by daily morphine administration.

Conclusions and implications: These data suggest that repeated administration of morphine increased effects of morphine on motor impulsivity, although tolerance developed to other effects, such as omissions. To the extent that impulsivity is a risk factor for drug abuse, repeated administration of μ opioid receptor agonists, for recreational or therapeutic purposes, might increase impulsivity and thus the risk for drug abuse.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Choice Behavior / drug effects*
  • Impulsive Behavior / drug effects*
  • Injections, Intraperitoneal
  • Male
  • Morphine / administration & dosage*
  • Morphine / pharmacology*
  • Rats
  • Rats, Sprague-Dawley
  • Reaction Time / drug effects

Substances

  • Morphine