title: Cholecystokinin octapeptide induces endogenous opioid-dependent anxiolytic effects in morphine-withdrawal rats.
abstract: 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.
authors.affiliation: Department of Forensic Medicine, Hebei Medical University, Hebei Key Laboratory of Forensic Medicine, Shijiazhuang 050017, PR China.
authors.forename: D
authors.initials: D
authors.lastname: Wen
authors.affiliation: Department of Forensic Medicine, Hebei Medical University, Hebei Key Laboratory of Forensic Medicine, Shijiazhuang 050017, PR China.
authors.forename: D
authors.initials: D
authors.lastname: Sun
authors.affiliation: Department of Forensic Medicine, Hebei Medical University, Hebei Key Laboratory of Forensic Medicine, Shijiazhuang 050017, PR China.
authors.forename: G
authors.initials: G
authors.lastname: Zang
authors.affiliation: Department of Forensic Medicine, Hebei Medical University, Hebei Key Laboratory of Forensic Medicine, Shijiazhuang 050017, PR China.
authors.forename: L
authors.initials: L
authors.lastname: Hao
authors.affiliation: Department of Forensic Medicine, Hebei Medical University, Hebei Key Laboratory of Forensic Medicine, Shijiazhuang 050017, PR China.
authors.forename: X
authors.initials: X
authors.lastname: Liu
authors.affiliation: Department of Forensic Medicine, Hebei Medical University, Hebei Key Laboratory of Forensic Medicine, Shijiazhuang 050017, PR China.
authors.forename: F
authors.initials: F
authors.lastname: Yu
authors.affiliation: Department of Forensic Medicine, Hebei Medical University, Hebei Key Laboratory of Forensic Medicine, Shijiazhuang 050017, PR China. Electronic address: chunlingma@126.com.
authors.forename: C
authors.initials: C
authors.lastname: Ma
authors.affiliation: Department of Forensic Medicine, Hebei Medical University, Hebei Key Laboratory of Forensic Medicine, Shijiazhuang 050017, PR China. Electronic address: hbydbincong@126.com.
authors.forename: B
authors.initials: B
authors.lastname: Cong
mesh_terms: D000818:Animals; D014151:Anti-Anxiety Agents / Q000494:pharmacology*; D001007:Anxiety / Q000188:drug therapy* / Q000503:physiopathology; D001570:Benzodiazepinones / Q000494:pharmacology; D002491:Central Nervous System Agents / Q000494:pharmacology; D020109:Devazepide / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D008297:Male; D009020:Morphine / Q000009:adverse effects / Q000494:pharmacology; D009021:Morphine Dependence / Q000188:drug therapy* / Q000503:physiopathology / Q000523:psychology; D009294:Narcotics / Q000009:adverse effects / Q000494:pharmacology; D018847:Opioid Peptides / Q000378:metabolism*; D010671:Phenylurea Compounds / Q000494:pharmacology; D011897:Random Allocation; D017208:Rats, Wistar; D011949:Receptors, Cholecystokinin / Q000037:antagonists & inhibitors / Q000378:metabolism; D017450:Receptors, Opioid, mu / Q000037:antagonists & inhibitors / Q000378:metabolism; D012844:Sincalide / Q000494:pharmacology*; D013375:Substance Withdrawal Syndrome / Q000188:drug therapy* / Q000503:physiopathology / Q000523:psychology
chemical_list: D014151:Anti-Anxiety Agents; D001570:Benzodiazepinones; D002491:Central Nervous System Agents; D009294:Narcotics; D018847:Opioid Peptides; D010671:Phenylurea Compounds; D011949:Receptors, Cholecystokinin; D017450:Receptors, Opioid, mu; C058121:L 365260; D009020:Morphine; D020109:Devazepide; D012844:Sincalide
keywords: CCK receptor; anxiety; cholecystokinin octapeptide; elevated plus-maze; morphine withdrawal