Cholecystokinin octapeptide induces endogenous opioid-dependent anxiolytic effects in morphine-withdrawal rats.
Neuroscience
; 277: 14-25, 2014 Sep 26.
Article
in En
| MEDLINE
| ID: mdl-24993476
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.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Anxiety
/
Sincalide
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Substance Withdrawal Syndrome
/
Anti-Anxiety Agents
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Opioid Peptides
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Morphine Dependence
Limits:
Animals
Language:
En
Journal:
Neuroscience
Year:
2014
Document type:
Article