Cholecystokinin octapeptide induces endogenous opioid-dependent anxiolytic effects in morphine-withdrawal rats.
Cholecystokinin octapeptide (CCK-8), a brain-gut peptide, plays an important role in several opioid addictive behaviors. We previously reported that CCK-8 attenuated the expression and reinstatement of morphine-induced conditioned place preference. The possible effects of CCK-8 on the negative affective components of drug abstinence are not clear. There are no studies evaluating the effect of CCK-8 on emotional symptoms, such as anxiety, in morphine-withdrawal animals. We investigated the effects of CCK-8 on the anxiety-like behavior in morphine-withdrawal rats using an elevated plus-maze. Morphine withdrawal elicited time-dependent anxiety-like behaviors with peak effects on day 10 (5 days after induction of morphine dependence). Treatment with CCK-8 (0.1 and 1 μg, i.c.v.) blocked this anxiety in a dose-dependent fashion. A CCK1 receptor antagonist (L-364,718, 10 μg, i.c.v.) blocked the effect of CCK-8. Mu-opioid receptor antagonism with CTAP (10 μg, i.c.v.) decreased the 'anxiolytic' effect. CCK-8 inhibited anxiety-like behaviors in morphine-withdrawal rats by up-regulating endogenous opioids via the CCK1 receptor in rats. This study clearly identifies a distinct function of CCK-8 and a potential medication target of central CCK1 receptors for drugs aimed at ameliorating drug addiction.
['Wen|D|D|', 'Sun|D|D|', 'Zang|G|G|', 'Hao|L|L|', 'Liu|X|X|', 'Yu|F|F|', 'Ma|C|C|', 'Cong|B|B|']
D000818:Animals D014151:Anti-Anxiety Agents D001007:Anxiety D001570:Benzodiazepinones D002491:Central Nervous System Agents D020109:Devazepide D004305:Dose-Response Relationship, Drug D008297:Male D009020:Morphine D009021:Morphine Dependence D009294:Narcotics D018847:Opioid Peptides D010671:Phenylurea Compounds D011897:Random Allocation D017208:Rats, Wistar D011949:Receptors, Cholecystokinin D017450:Receptors, Opioid, mu D012844:Sincalide D013375:Substance Withdrawal Syndrome
cholecystokinin octapeptide anxiety elevated plus-maze morphine withdrawal CCK receptor