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

• Published in: British journal of pharmacology Vol. 173; no. 8; pp. 1350 - 1362
• Main Authors: Maguire, DR, Henson, C, France, CP
• Format: Journal Article
• Language: English
• Published: England Blackwell Publishing Ltd 01-04-2016; John Wiley and Sons Inc
• Subjects: Amphetamines; Animals; Choice Behavior - drug effects; Drug abuse; Drug tolerance; Impulsive behavior; Impulsive Behavior - drug effects; Impulsivity; Injections, Intraperitoneal; Male; Morphine; Morphine - administration & dosage; Morphine - pharmacology; Narcotics; Opioid receptors; Rats; Rats, Sprague-Dawley; Reaction Time - drug effects; Reaction time task; Research Paper; Research Papers; Risk factors; Therapeutic applications
• ISSN: 0007-1188; 1476-5381
• DOI: 10.1111/bph.13434

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.