The novel dopamine D3 receptor antagonist, SR 21502, reduces cocaine conditioned place preference in rats.
Research has shown that dopamine (DA) D3 receptors play a crucial role in cocaine addiction. Recently, there has been a strong focus on the development of DA D3 receptor antagonists as potential pharmacological treatments for cocaine addiction. We investigated the ability of a novel selective D3 receptor antagonist SR 21502 to block the expression of cocaine-induced conditioned place preference (CPP) in rats. CPP was determined using a two-chamber apparatus. All of the animals had free access to both chambers on day 1, followed by 4 alternating conditioning days of cocaine injection (paired chamber) and 4 alternating non-conditioning days with saline (non-paired chamber). On the test day, animals were systemically treated with 0, 3.75, 7.5 or 15mg/kg of SR 21502, 10min prior to being placed in the CPP apparatus, and the time spent in each chamber was recorded for 15min. The amount of time spent in the cocaine-paired chamber on the test and pre-exposure days was analyzed. Vehicle-treated animals spent significantly more time in the cocaine-paired side during the test than during the pre-exposure session, indicating a cocaine CPP. SR 21502 produced a dose-related significant reduction in the time spent in the cocaine-paired side compared to vehicle. The DA D3 receptor antagonist SR 21502 blocks the rat's preference for the cocaine-paired chamber, thereby attenuating the rewarding effect of the cocaine cues. This suggests that this compound may be an effective pharmacological treatment against cocaine addiction.
CUNY Graduate Center, Neuropsychology Doctoral Program, United States.
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Hachimine
Queens College of the City University of New York, Department of Psychology, United States.
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Seepersad
Organic Chemistry Department, Southern Research Institute, United States.
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Ananthan
CUNY Graduate Center, Neuropsychology Doctoral Program, United States; Queens College of the City University of New York, Department of Psychology, United States. Electronic address: Robert.Ranaldi@qc.cuny.edu.
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Ranaldi
D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D003042:Cocaine / Q000494:pharmacology*; D003214:Conditioning, Classical / Q000187:drug effects*; D003463:Cues; D065127:Dopamine D2 Receptor Antagonists / Q000494:pharmacology*; D058999:Drug-Seeking Behavior / Q000187:drug effects*; D007093:Imidazoles / Q000494:pharmacology*; D008297:Male; D011725:Pyridines / Q000494:pharmacology*; D020318:Rats, Long-Evans; D012201:Reward
D065127:Dopamine D2 Receptor Antagonists; D007093:Imidazoles; D011725:Pyridines; C000593313:SR 21502; D003042:Cocaine
Addiction; Cocaine; Conditioned place preference; D3 receptor antagonist