Acute effects of morphine on distinct forms of impulsive behavior in rats.
BACKGROUND
Disturbances in impulse control are key features of substance abuse disorders, and conversely, many drugs of abuse are known to elicit impulsive behavior both clinically and preclinically. To date, little is known with respect to the involvement of the opioid system in impulsive behavior, although recent findings have demonstrated its involvement in delay discounting processes. The aim of the present study was to further investigate the role of the opioid system in varieties of impulsivity.


METHODS
To this end, groups of rats were trained in the five-choice serial reaction time task (5-CSRTT) and stop-signal task (SST), operant paradigms that provide measures of inhibitory control and response inhibition, respectively. In addition, another group of rats was trained in the delayed reward paradigm, which measures the sensitivity towards delay of gratification and as such assesses impulsive choice.


CONCLUSIONS
Results demonstrated that morphine, a selective micro-opioid receptor agonist, primarily impaired inhibitory control in the 5-CSRTT by increasing premature responding. In addition, in keeping with previous data, morphine decreased the preference for the large over small reward in the delayed reward paradigm. The effects of morphine on measures of impulsivity in both the 5-CSRTT and delayed reward paradigm were blocked by naloxone, a micro-opioid receptor antagonist. Naloxone by itself did not alter impulsive behavior, suggesting limited involvement of an endogenous opioid tone in impulsivity. Response inhibition measured in the SST was neither altered by morphine nor naloxone, although some baseline-dependent effects of morphine on response inhibition were observed.


CONCLUSIONS
In conclusion, the present data demonstrate that acute challenges with morphine modulate distinct forms of impulsive behavior, thereby suggesting a role for the opioid system in impulsivity.
Pattij
Tommy
T
Department of Anatomy and Neurosciences, Neuroscience Campus Amsterdam, Center for Neurogenomics and Cognitive Research, VU University Medical Center, Van der Boechorststraat 7, 1081 BT Amsterdam, The Netherlands. t.pattij@vumc.nl
Schetters
Dustin
D
Janssen
Mieke C W
MC
Wiskerke
Joost
J
Schoffelmeer
Anton N M
AN
D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D002755:Choice Behavior / Q000187:drug effects*; D003216:Conditioning, Operant / Q000187:drug effects; D007175:Impulsive Behavior / Q000523:psychology*; D008297:Male; D009020:Morphine / Q000008:administration & dosage / Q000494:pharmacology*; D009270:Naloxone / Q000494:pharmacology; D009292:Narcotic Antagonists / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D011930:Reaction Time / Q000187:drug effects*; D017450:Receptors, Opioid, mu / Q000819:agonists / Q000037:antagonists & inhibitors; D012201:Reward
D009292:Narcotic Antagonists; D017450:Receptors, Opioid, mu; D009270:Naloxone; D009020:Morphine