Conditioned Reinforcing Effects of a Remifentanil-Paired Stimulus in the Rat.

When environmental stimuli are paired with a primary reinforcer (e.g., food, certain drugs), these stimuli may become conditioned reinforcers capable of maintaining behavior in the absence of the primary reinforcer. Drug-associated conditioned reinforcers are thought to contribute significantly to human drug abuse and dependence; however, few studies have characterized specifically the conditioned reinforcing effects of drug-paired stimuli, controlling for other, confounding associative and nonassociative processes that can change behavior. The present experiments, therefore, assessed the conditioned reinforcing effects of a stimulus paired with the potent, short-acting mu-opioid agonist, remifentanil, using a behaviorally stringent new-response acquisition procedure. First, in Pavlovian conditioning (PAV) sessions, rats received response-independent IV injections of remifentanil and presentations of a light-noise stimulus. In paired PAV groups, injections and stimulus presentations always co-occurred. In random PAV control groups, injections and stimulus presentations occurred independently of each other. Next, in instrumental acquisition (ACQ) test sessions, rats could respond in an active nose-poke that produced the stimulus alone or an inactive nose-poke that had no scheduled consequences. Rats acquired nose-poking (i.e., active > inactive) after paired PAV, but not random PAV. These results show responding was (1) not due to association of the nose-poke with remifentail, (2) sensitive to the Pavlovian contingency between the stimulus and remifentanil, and (3) sensitive to the instrumental contingency between a nose-poke and the stimulus. After, thus, validating the behavioral procedure, the effects of the dopamine D3 receptor-preferring agonist, pramipexole, on responding with the remifentanil-paired stimulus was assessed. Dopamine D2-like receptor agonists can enhance new-response acquisition with food-paired conditioned reinforcers, but this effect has not, to my knowledge, been previously demonstrated with drug-paired stimuli. When pretreatments of saline or pramipexole were given before ACQ sessions, pramipexole dose-dependently increased active responding without changing inactive responding. Control animals given pramixpole after random PAV did not acquire nose-poking. The response-enhancing effects of pramipexole were attenuated by the D2 receptor-preferring antagonist, L-741,626, but not the D3 receptor-preferring antagonist, SB-277011A. D2 activity may, therefore, be particularly important for responding with conditioned reinforcement. Together, these experiments demonstrate that new-response acquisition can provide a valid, practically useful measure of opioid-associated conditioned reinforcement.PhDPsychologyUniversity of Michigan, Horace H. Rackham School of Graduate Studieshttp://deepblue.lib.umich.edu/bitstream/2027.42/99853/1/jwbertz_1.pd