Acute administration of SB-277011A, NGB 2904, or BP 897 inhibits cocaine cue-induced reinstatement of drug-seeking behavior in rats: role of dopamine D3 receptors.
Recent studies have shown that the novel dopamine (DA) D3 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 D3 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 D3 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 D3 and non-D3 receptor mechanisms.
Gilbert
Jeremy G
JG
Neuropsychopharmacology Section, Behavioral Neuroscience Research Branch, Intramural Research Program, National Institute on Drug Abuse, National Institutes of Health, DHHS, Baltimore, Maryland 21224, USA.
Newman
Amy Hauck
AH
Gardner
Eliot L
EL
Ashby
Charles R
CR
Heidbreder
Christian A
CA
Pak
Arlene C
AC
Peng
Xiao-Qing
XQ
Xi
Zheng-Xiong
ZX
D000818:Animals; D003042:Cocaine / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D019970:Cocaine-Related Disorders / Q000188:drug therapy / Q000523:psychology*; D003216:Conditioning, Operant / Q000187:drug effects; D003463:Cues; D018492:Dopamine Antagonists / Q000494:pharmacology*; D065127:Dopamine D2 Receptor Antagonists; D005108:Extinction, Psychological / Q000187:drug effects; D005449:Fluorenes / Q000494:pharmacology*; D008297:Male; D009570:Nitriles / Q000494:pharmacology*; D010775:Photic Stimulation; D010879:Piperazines / Q000494:pharmacology*; D051381:Rats; D020318:Rats, Long-Evans; D050637:Receptors, Dopamine D3; D012008:Recurrence; D012646:Self Administration; D044005:Tetrahydroisoquinolines / Q000494:pharmacology*
D018492:Dopamine Antagonists; D065127:Dopamine D2 Receptor Antagonists; C493595:Drd3 protein, rat; D005449:Fluorenes; C116818:NGB 2904; D009570:Nitriles; D010879:Piperazines; D050637:Receptors, Dopamine D3; C409982:SB 277011; D044005:Tetrahydroisoquinolines; C120565:BP 897; D003042:Cocaine