Inhibition of anxiety in rats by antisense to cholecystokinin precursor protein.
BACKGROUND
Cholecystokinin (CCK) and its analogs generates anxiety in humans and measurable anxiety-like behaviors in rats. CCK receptor blockers have had mixed results as a treatment approach for anxiety disorders. Since CCK is a peptide, we explored another strategy to reduce CCK levels in brain by antisense oligodeoxynucleotide inhibition of DNA transcription or messenger RNA (mRNA) translation for CCK precursor protein.


METHODS
Antisense oligodeoxynucleotide complementary to the start coding region of rat CCK-precursor was intracerebroventricularly (icv) infused into rats three times at 24-hour intervals. Control groups received infusions of either a scramble sequence oligodeoxynucleotide or vehicle. On the fourth day, rats were assessed in the elevated plus maze paradigm.


RESULTS
Compared to vehicle and scramble sequence oligodeoxynucleotide control, icv CCK-antisense exogenous administration for 3 days significantly diminished anxiety behavior in rats.


CONCLUSIONS
Antisense inhibition of CCK-mediated anxiety could have therapeutic potential in human anxiety disorders.
Cohen
H
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.
Kaplan
Z
Z
Kotler
M
M
D000818:Animals; D001007:Anxiety / Q000188:drug therapy* / Q000503:physiopathology; D002766:Cholecystokinin / Q000187:drug effects* / Q000502:physiology; D004334:Drug Administration Schedule; D005106:Exploratory Behavior / Q000187:drug effects; D007275:Injections, Intravenous; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D020319:Oligodeoxyribonucleotides, Antisense / Q000494:pharmacology*; D011498:Protein Precursors / Q000187:drug effects* / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley
D020319:Oligodeoxyribonucleotides, Antisense; D011498:Protein Precursors; C060249:procholecystokinin; D002766:Cholecystokinin