PMID- 9807648 OWN - NLM STAT- MEDLINE DCOM- 19990504 LR - 20190815 IS - 0006-3223 (Print) IS - 0006-3223 (Linking) VI - 44 IP - 9 DP - 1998 Nov 1 TI - Inhibition of anxiety in rats by antisense to cholecystokinin precursor protein. PG - 915-7 AB - 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. FAU - Cohen, H AU - Cohen H AD - Ministry of Health Mental Health Center, Faculty of Health Sciences, Anxiety and Stress Research Unit, Ben Gurion University of the Negev, Beer-Sheva, Israel. FAU - Kaplan, Z AU - Kaplan Z FAU - Kotler, M AU - Kotler M LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - United States TA - Biol Psychiatry JT - Biological psychiatry JID - 0213264 RN - 0 (Oligodeoxyribonucleotides, Antisense) RN - 0 (Protein Precursors) RN - 78206-77-6 (procholecystokinin) RN - 9011-97-6 (Cholecystokinin) SB - IM MH - Animals MH - Anxiety/*drug therapy/physiopathology MH - Cholecystokinin/*drug effects/physiology MH - Drug Administration Schedule MH - Exploratory Behavior/drug effects MH - Injections, Intravenous MH - Male MH - Maze Learning/drug effects MH - Oligodeoxyribonucleotides, Antisense/*pharmacology MH - Protein Precursors/*drug effects/physiology MH - Rats MH - Rats, Sprague-Dawley EDAT- 1998/11/10 00:00 MHDA- 1998/11/10 00:01 CRDT- 1998/11/10 00:00 PHST- 1998/11/10 00:00 [pubmed] PHST- 1998/11/10 00:01 [medline] PHST- 1998/11/10 00:00 [entrez] AID - S0006-3223(98)00010-9 [pii] AID - 10.1016/s0006-3223(98)00010-9 [doi] PST - ppublish SO - Biol Psychiatry. 1998 Nov 1;44(9):915-7. doi: 10.1016/s0006-3223(98)00010-9.