Abstract
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.
| Original language | English |
|---|---|
| Pages (from-to) | 915-917 |
| Number of pages | 3 |
| Journal | Biological Psychiatry |
| Volume | 44 |
| Issue number | 9 |
| DOIs | |
| State | Published - 1 Nov 1998 |
| Externally published | Yes |
Keywords
- Animal model
- Antisense oligodeoxynucleotide
- Anxiety
- Cholecystokinin