Effect of intraperitoneal mRNA antisense-oligodeoxynucleotides to cholecystokinin on anxiety-like and learning behaviors in rats: association with pre-experimental stress.
BACKGROUND
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.
Cohen
Hagit
H
Ministry of Health Mental Health Center, Faculty of Health Sciences, Anxiety and Stress Research Unit, Ben Gurion University of the Negev, Beer-Sheva, Israel. hagitc@bgumail.bgu.ac.il
Matar
Michael A
MA
Buriakovsky
Igor
I
Zeev
Kaplan
K
Kotler
Moshe
M
Bourin
Michel
M
D000818:Animals; D001007:Anxiety / Q000139:chemically induced* / Q000378:metabolism; D002766:Cholecystokinin / Q000009:adverse effects* / Q000819:agonists*; D007274:Injections, Intraperitoneal; D008297:Male; D018782:Maze Learning / Q000187:drug effects*; D020319:Oligodeoxyribonucleotides, Antisense / Q000008:administration & dosage / Q000009:adverse effects*; D051381:Rats; D011919:Rats, Inbred Strains; D013315:Stress, Psychological / Q000378:metabolism*; D014867:Water
D020319:Oligodeoxyribonucleotides, Antisense; D014867:Water; D002766:Cholecystokinin