The effects of the novel DA D3 receptor antagonist SR 21502 on cocaine reward, cocaine seeking and cocaine-induced locomotor activity in rats

• Published in: Psychopharmacology Vol. 231; no. 3; pp. 501 - 510
• Main Authors: Galaj, E., Ananthan, S., Saliba, M., Ranaldi, Robert
• Format: Journal Article
• Language: English
• Published: Berlin/Heidelberg Springer Berlin Heidelberg 01-02-2014; Springer; Springer Nature B.V
• Subjects: Addictive behaviors; Analysis; Animal locomotion; Animals; Biomedical and Life Sciences; Biomedicine; Cellular proteins; Cocaine; Cocaine - adverse effects; Cocaine-Related Disorders - drug therapy; Cues; Dopamine Antagonists - chemistry; Dopamine Antagonists - pharmacology; Dopamine Uptake Inhibitors - adverse effects; Dose-Response Relationship, Drug; Drug abuse; Drug-Seeking Behavior - drug effects; Extinction, Psychological - drug effects; Feeding Behavior - drug effects; Genetic research; Imidazoles - chemistry; Imidazoles - pharmacology; Male; Motor Activity - drug effects; Neurosciences; Original Investigation; Pharmacology/Toxicology; Psychiatry; Psychopharmacology; Pyridines - chemistry; Pyridines - pharmacology; Random Allocation; Rats, Long-Evans; Receptors, Dopamine D3 - antagonists & inhibitors; Reinforcement (Psychology); Self Administration; United States > US; D3 receptor; Food reward; Relapse; Reward; Locomotor activity
• ISSN: 0033-3158; 1432-2072
• DOI: 10.1007/s00213-013-3254-y

Rationale
There is a focus on developing D3 receptor antagonists as cocaine addiction treatments.
Objective
We investigated the effects of a novel selective D3 receptor antagonist, SR 21502, on cocaine reward, cocaine-seeking, food reward, spontaneous locomotor activity and cocaine-induced locomotor activity in rats.
Methods
In Experiment 1, rats were trained to self-administer cocaine under a progressive ratio (PR) schedule of reinforcement and tested with vehicle or one of three doses of SR 21502. In Experiment 2, animals were trained to self-administer cocaine under a fixed ratio schedule of reinforcement followed by extinction of the response. Then, animals were tested with vehicle or one of the SR 21502 doses on cue-induced reinstatement of responding. In Experiment 3, animals were trained to lever press for food under a PR schedule and tested with vehicle or one dose of the compound. In Experiments 4 and 5, in separate groups of animals, the vehicle and three doses of SR 21502 were tested on spontaneous or cocaine (10 mg/kg, IP)-induced locomotor activity, respectively.
Results
SR 21502 produced significant, dose-related (3.75, 7.5 and 15 mg/kg) reductions in breakpoint for cocaine self-administration, cue-induced reinstatement (3.75, 7.5 and 15 mg/kg) and cocaine-induced locomotor activity (3.75, 7.5 and 15 mg/kg) but failed to reduce food self-administration and spontaneous locomotor activity.
Conclusions
SR 21502 decreases cocaine reward, cocaine-seeking and locomotor activity at doses that have no effect on food reward or spontaneous locomotor activity. These data suggest SR 21502 may selectively inhibit cocaine’s rewarding, incentive motivational and stimulant effects.