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Effect of intraperitoneal mRNA antisense-oligodeoxynucleotides to cholecystokinin on anxiety-like and learning behaviors in rats: association with pre-experimental stress.

Authors: Cohen, H  Matar, MA  Buriakovsky, I  Zeev, K  Kotler, M  Bourin, M 
Citation: Cohen H, etal., Neuropeptides. 2002 Oct;36(5):341-52.
Pubmed: (View Article at PubMed) PMID:12450740

RATIONALE: Cholecystokinin and its analogs generate anxiety in humans and measurable anxiety-like behaviors in rats. Cholecystokinin receptor blockers have been reported to have variable effects in the treatment of anxiety disorders. We demonstrated that intracerebroventricular administration of Cholecystokinin-antisense oligodeoxynucleotides (ASODN) for 3 days significantly diminished anxiety-like behavior in rats. OBJECTIVE: This study was designed to examine the effects of peripheral (intraperitoneal) administration of Cholecystokinin-ASODN on anxiety-like and learning behaviors in rats, in general and in a pre-experiment stress paradigm. METHODS: In the first study Cholecystokinin-ASODN was injected intraperitoneally to rats five times at 24-h intervals. Control groups received injections of either a scrambled oligodeoxynucleotide (ScrODN) or vehicle. On the sixth day, the rats were assessed in the elevated plus-maze paradigm and in the Morris water maze. In the second study, rats were pre-exposed to a cat for 10 min as a model for psychological stress, and then treated with intraperitoneal Cholecystokinin-ASODN and tested in both paradigms. RESULTS: The results show that for intact rats, intraperitoneal Cholecystokinin-ASODN significantly increased anxiety-like behavior and impaired retention performance in the Morris water maze, compared to both control groups. In stressed rats, Cholecystokinin-ASODN reduced anxiety-like behaviors in the plus-maze and improved performance in the water maze compared with controls. CONCLUSIONS: These results indicate that the anxiolytic effect of intraperitoneal Cholecystokinin-ASODN may be dependent on the baseline endogenous level of stress (i.e., on the Cholecystokinin levels). Basal endogenous levels of Cholecystokinin, as well as exogenous dosage of Cholecystokinin agonists and/or anxiolytic agents, appear to play an important role in the expression and/or control of anxiety-related behaviors in rats.

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CRRD Object Information
CRRD ID: 1626100
Created: 2007-07-11
Species: All species
Last Modified: 2007-07-11
Status: ACTIVE



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RGD is funded by grant HL64541 from the National Heart, Lung, and Blood Institute on behalf of the NIH.