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Published on: November 6, 2018
Daily morphine administration increases impulsivity in rats responding under a 5-choice serial reaction time task
D R Maguire1, C Henson1, C P France1,2
1Department of Pharmacology, University of Texas Health Science Center at San Antonio, San Antonio, Texas, USA.
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.
Insights
Repeated morphine administration increased motor impulsivity in rats, a key factor in drug abuse risk. Tolerance developed to other effects, but motor impulsivity worsened with daily opioid agonist use.
Area of Science:
- Neuroscience
- Behavioral Pharmacology
Background:
- Opioid agonists, like morphine, can increase impulsivity, particularly delay discounting.
- The impact of repeated opioid agonist administration on motor impulsivity remains largely unexamined.
Purpose of the Study:
- To investigate the effects of acute and repeated morphine administration on motor impulsivity in rats.
- To assess whether tolerance develops to the motor impulsivity-enhancing effects of morphine.
Main Methods:
- Rats were trained on a five-choice serial reaction time task, with premature responding serving as the index of motor impulsivity.
- The effects of acute morphine and amphetamine were assessed before and during daily morphine administration over three weeks.
Main Results:
- Acute morphine increased omissions and premature responding; amphetamine increased premature responding.
- Following three weeks of daily morphine, tolerance developed to its effects on omissions.
- Motor impulsivity, measured by premature responding, significantly increased with repeated morphine administration.
Conclusions:
- Repeated morphine administration enhances motor impulsivity, despite tolerance to other effects.
- Increased impulsivity due to opioid agonist use may elevate the risk for drug abuse.
