title: The effects of exogenous CCK-8 on the acquisition and expression of morphine-induced CPP.
abstract: Cholecystokinin octapeptide (CCK-8) is the most potent endogenous anti-opioid peptide and regulates a variety of physiological processes. In our previous study, we found that exogenous CCK-8 attenuated naloxone-induced withdrawal symptoms, but the possible regulative effects of CCK-8 on the rewarding effects of morphine were not examined. In the present study, we aimed to determine the exact effects of exogenous CCK-8 at various doses on the rewarding action of morphine by utilizing the unbiased conditioned place preference (CPP) paradigm. We therefore examined the effects of CCK-8 on the acquisition, expression and extinction of morphine-induced CPP and on locomotor activity. The results showed that CCK-8 (0.01-1μg, i.c.v.), administered alone, induced neither CPP nor place aversion, but blocked the acquisition of CPP when administered with 10mg/kg morphine. The highest dose of CCK-8 (1μg) administered before CPP testing increased CPP and, along with lower doses (0.1μg), reduced its extinction. In addition, the highest dose (1μg) of CCK-8 suppressed locomotor activity. Our study provides the first behavioral evidence for the inhibitory effects of exogenous CCK-8 on rewarding activity and reveals significant effects of exogenous CCK-8 on various stages of place preference and the development of opioid dependence.
authors.affiliation: Department of Forensic Medicine, Hebei Medical University, Hebei Key Laboratory of Forensic Medicine, Shijiazhuang 050017, PR China.
authors.forename: Di
authors.initials: D
authors.lastname: Wen
authors.forename: Bin
authors.initials: B
authors.lastname: Cong
authors.forename: Chunling
authors.initials: C
authors.lastname: Ma
authors.forename: Shengchang
authors.initials: S
authors.lastname: Yang
authors.forename: Hailei
authors.initials: H
authors.lastname: Yu
authors.forename: Zhiyu
authors.initials: Z
authors.lastname: Ni
authors.forename: Shujin
authors.initials: S
authors.lastname: Li
mesh_terms: D000701:Analgesics, Opioid / Q000494:pharmacology*; D000818:Animals; D001362:Avoidance Learning / Q000187:drug effects; D003213:Conditioning, Psychological / Q000187:drug effects* / Q000502:physiology*; D004305:Dose-Response Relationship, Drug; D005108:Extinction, Psychological / Q000187:drug effects / Q000502:physiology; D008297:Male; D009020:Morphine / Q000494:pharmacology*; D009043:Motor Activity / Q000187:drug effects; D009293:Opioid-Related Disorders / Q000188:drug therapy / Q000209:etiology / Q000503:physiopathology; D051381:Rats; D017208:Rats, Wistar; D012201:Reward; D012844:Sincalide / Q000008:administration & dosage / Q000494:pharmacology*; D013375:Substance Withdrawal Syndrome / Q000188:drug therapy / Q000209:etiology / Q000503:physiopathology
chemical_list: D000701:Analgesics, Opioid; D009020:Morphine; D012844:Sincalide