title: Subanesthetic ketamine decreases the incentive-motivational value of reward-related cues.
abstract: The attribution of incentive-motivational value to reward-related cues contributes to cue-induced craving and relapse in addicted patients. Recently, it was demonstrated that subanesthetic ketamine increases motivation to quit and decreases cue-induced craving in cocaine-dependent individuals. Although the underlying mechanism of this effect is currently unknown, one possibility is that subanesthetic ketamine decreases the incentive-motivational value of reward-related cues. In the present study, we used a Pavlovian conditioned approach procedure to identify sign-trackers, rats that attribute incentive-motivational value to reward-related cues, and goal-trackers, rats that assign only predictive value to reward-related cues. This model is of interest because sign-trackers are more vulnerable to cue-induced reinstatement of drug-seeking behavior and will persist in this drug-seeking behavior despite adverse consequences. We tested the effect of subanesthetic ketamine on the expression of Pavlovian conditioned approach behavior and the conditioned reinforcing properties of a reward-related cue in sign- and goal-trackers. We found that subanesthetic ketamine decreased sign-tracking and increased goal-tracking behavior in sign-trackers, though it had no effect on conditioned reinforcement. These results suggest that subanesthetic ketamine may be a promising pharmacotherapy for addiction that acts by decreasing the incentive-motivational value of reward-related cues.
authors.affiliation: 1 Neuroscience Graduate Program, University of Michigan, Ann Arbor, USA.
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Fitzpatrick
authors.affiliation: 1 Neuroscience Graduate Program, University of Michigan, Ann Arbor, USA.|2 Department of Psychiatry, University of Michigan, Ann Arbor, USA.
authors.forename: Jonathan D
authors.initials: JD
authors.lastname: Morrow
mesh_terms: D000818:Animals; D016739:Behavior, Addictive / Q000188:drug therapy*; D003042:Cocaine / Q000494:pharmacology; D003214:Conditioning, Classical / Q000187:drug effects; D003463:Cues; D058999:Drug-Seeking Behavior / Q000187:drug effects*; D007649:Ketamine / Q000494:pharmacology*; D008297:Male; D009042:Motivation / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012054:Reinforcement, Psychology; D012201:Reward
chemical_list: D007649:Ketamine; D003042:Cocaine
keywords: Pavlovian conditioned approach; addiction; conditioned reinforcement; salience; sign-tracking