Abstract:
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.
journal_name
Neuropeptidesjournal_title
Neuropeptidesauthors
Cohen H,Matar MA,Buriakovsky I,Zeev K,Kotler M,Bourin Mdoi
10.1016/s0143-4179(02)00088-4keywords:
subject
Has Abstractpub_date
2002-10-01 00:00:00pages
341-52issue
5eissn
0143-4179issn
1532-2785pii
S0143417902000884journal_volume
36pub_type
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