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Acute administration of SB‐277011A, NGB 2904, or BP 897 inhibits cocaine cue‐induced reinstatement of drug‐seeking behavior in rats: Role of dopamine D 3 receptors
Author(s) -
Gilbert Jeremy G.,
Newman Amy Hauck,
Gardner Eliot L.,
Ashby Charles R.,
Heidbreder Christian A.,
Pak Arlene C.,
Peng XiaoQing,
Xi ZhengXiong
Publication year - 2005
Publication title -
synapse
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.809
H-Index - 106
eISSN - 1098-2396
pISSN - 0887-4476
DOI - 10.1002/syn.20152
Subject(s) - pharmacology , self administration , dopamine , antagonist , extinction (optical mineralogy) , drug , antagonism , agonist , medicine , psychology , receptor , chemistry , mineralogy
Recent studies have shown that the novel dopamine (DA) D 3 receptor antagonists SB‐277011A and NGB 2904 inhibit cocaine‐ and/or stress‐induced reinstatement of drug‐seeking behavior. The present study sought to determine if SB‐277011A, NGB 2904, or BP‐897 (a mixed D 3 agonist/antagonist) similarly inhibit cocaine‐associated cue‐induced reinstatement of drug‐seeking behavior. Long‐Evans rats were allowed to self‐administer cocaine. Each cocaine infusion was paired with discrete conditioned cue‐light and tone. Subsequently, drug‐seeking (i.e., lever‐pressing) behavior was extinguished in the absence of cocaine and cocaine‐associated cues. Rats were then tested for cue‐induced reinstatement of drug‐seeking. We found that cocaine‐associated cues evoked robust reinstatement of lever‐pressing. Acute intraperitoneal (i.p.) administration of SB‐277011A (6, 12, or 24 mg/kg) produced a dose‐dependent inhibition of cue‐induced reinstatement of drug‐seeking behavior by 35, 65, and 85%, respectively, compared to vehicle‐treated animals. Acute i.p. administration of NGB 2904 (0.1, 1.0, or 5.0 mg/kg) produced a 45, 30, and 70% inhibition of cue‐induced reinstatement, respectively, compared to vehicle‐treated animals. Acute i.p. administration of either 0.1 or 1 mg/kg of BP 897 did not produce a significant effect on cue‐induced reinstatement, whereas a dose of 3 mg/kg produced a 70% inhibition of cue‐induced reinstatement. These findings, combined with previous data, suggest that DA D 3 receptor antagonism may underlie the inhibitory effects of SB‐277011A and NGB 2904 on cocaine cue‐induced reinstatement, while the effects of BP 897 may involve D 3 and non‐D 3 receptor mechanisms. Synapse 57:17–28, 2005. Published 2005 Wiley‐Liss, Inc.