Reactivation of cocaine conditioned place preference induced by stress is reversed by cholecystokinin-B receptors antagonist in rats.
The effects of different cholecystokinin (CCK) receptor antagonists (devazepide and L365,260) on cocaine or stress-induced reactivation of cocaine conditioned place preference (CPP) were investigated in rats. After receiving alternate injection of cocaine (10 mg/kg) and saline for 8 consecutive days, the rats spent more time in the drug-paired side (cocaine CPP) on day 9. These animals did not show cocaine CPP on day 31 following saline-paired training daily from days 10 to 30 (21-day extinction). However, a single injection of cocaine (10 mg/kg) or 15 min of intermittent footshock could reinstate CPP on day 32 with significant more time spent in the drug-paired side in comparison with that on day 0. Systemic injection of CCK-A receptor antagonists, devazepide (0.1 and 1 mg/kg, i.p.), 30 min before cocaine priming, significantly attenuated cocaine-induced reinstatement of CPP, while CCK-B receptor antagonist, L365,260 (0.1 and 1 mg/kg, i.p.), did not show a similar effect. In contrast, pretreatment with L365,260 (0.1 and 1 mg/kg, i.p.) but not devazepide (0.1 and 1 mg/kg, i.p.) significantly blocked stress-induced reinstatement of CPP. In another experiment, CCK-A or B receptor antagonists were infused into nucleus accumbens or amygdala to determine which brain area are involved in the role of different CCK receptors in stress or drug-induced relapse to cocaine seeking. The results show that infusion of the devazepide (10 microg) into the nucleus accumbens significantly inhibited the cocaine-induced reinstatement of CPP, while infusion of devazepide (1 and 10 microg) into amygdala did not affect cocaine-induced reactivation of CPP. Interestingly, infusion of L365,260 (1 and 10 microg) into both nucleus accumbens or amygdala significantly attenuated or blocked stress-induced reinstatement of CPP. These findings demonstrate that CCK-A and B receptor have different roles in relapse to drug craving and further suggest that the brain areas involved in the CCK receptors on reinstatement of drug seeking are not identical. CCK-B receptor antagonists might be of some value in the treatment and prevention of relapse to stress-induced to drug craving following long-term detoxification.
Lu
Lin
L
Kailuan Mental Health Center, Tangshan 063001, China. llu@intra.nida.nih.gov
Zhang
Ben
B
Liu
Zhiyuan
Z
Zhang
Zhanyin
Z
D000818:Animals; D001570:Benzodiazepinones / Q000008:administration & dosage / Q000494:pharmacology; D001921:Brain / Q000187:drug effects; D003042:Cocaine / Q000494:pharmacology*; D003216:Conditioning, Operant / Q000187:drug effects*; D020109:Devazepide / Q000008:administration & dosage / Q000494:pharmacology; D006727:Hormone Antagonists / Q000008:administration & dosage / Q000494:pharmacology*; D007276:Injections, Intraventricular; D008297:Male; D010671:Phenylurea Compounds / Q000008:administration & dosage / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D011949:Receptors, Cholecystokinin / Q000037:antagonists & inhibitors*; D013312:Stress, Physiological / Q000503:physiopathology*
D001570:Benzodiazepinones; D006727:Hormone Antagonists; D010671:Phenylurea Compounds; D011949:Receptors, Cholecystokinin; C058121:L 365260; D003042:Cocaine; D020109:Devazepide