Priming with BTCP, a dopamine reuptake blocker, reinstates cocaine-seeking and enhances cocaine cue-induced reinstatement.
N-[1-(2-benzo[b]thiophenyl)cyclohexyl]piperidine (BTCP), a potent dopamine reuptake inhibitor, substitutes for the reinforcing effects of cocaine and meets other criteria for possible agonist pharmacotherapeutic potential. The purpose of this study was to determine (1) whether BTCP modifies reinstatement of cocaine-seeking elicited by cocaine-related environmental stimuli and (2) whether this compound produces priming effects. Male Wistar rats were trained to associate discriminative stimuli (S(D)) with cocaine availability (0.25 mg/infusion) versus non-reward and then were subjected to repeated extinction sessions during which the reinforcer and S(D) were withheld. Subsequent presentation of the cocaine S(D) produced recovery of cocaine-seeking. BTCP (2.5-30 mg/kg; i.p.) did not attenuate the conditioned reinstatement induced by the cocaine S(D) but, rather, potentiated this effect at 10 mg/kg. To test whether BTCP, by itself, exerts priming effects, different groups of rats were trained to self-administer cocaine (0.25 mg/infusion) for 2 weeks. After a 2-week extinction period, BTCP (5, 10 and 20 mg/kg, i.p.) reinstated cocaine-seeking, showing that BTCP not only increases cocaine-seeking induced by cocaine-related stimuli but also produces priming effects following abstinence. The results suggest that, in cocaine abstinent rats, BTCP produces cocaine-like effects.
Martin-Fardon
Rémi
R
The Scripps Research Institute, Department of Neuropharmacology, CVN-15, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA. rmartinf@scripps.edu
Lorentz
Christina U
CU
Stuempfig
Nathan D
ND
Weiss
Friedbert
F
D000818:Animals; D003042:Cocaine / Q000494:pharmacology*; D003216:Conditioning, Operant; D018765:Dopamine Uptake Inhibitors / Q000494:pharmacology*; D008297:Male; D009042:Motivation; D010622:Phencyclidine / Q000031:analogs & derivatives* / Q000494:pharmacology; D051381:Rats
D018765:Dopamine Uptake Inhibitors; C056415:1-(1-(2-benzo(b)thienyl)cyclohexyl)piperidine; D003042:Cocaine; D010622:Phencyclidine