Journal
NEUROSCIENCE
Volume 277, Issue -, Pages 14-25Publisher
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.neuroscience.2014.06.048
Keywords
cholecystokinin octapeptide; CCK receptor; morphine withdrawal; anxiety; elevated plus-maze
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Funding
- Natural Science Foundation of China [81302618, 81273337, 81172900]
- Training Funds for Talent Project in Hebei Province
- Natural Science Foundation of Hebei Province [H2013206157]
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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 mu g, i.c.v.) blocked this anxiety in a dose-dependent fashion. A CCK1 receptor antagonist (L-364,718, 10 mu g, i.c.v.) blocked the effect of CCK-8. Mu-opioid receptor antagonism with CTAP (10 mu g, 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. (C) 2014 IBRO. Published by Elsevier Ltd. All rights reserved.
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