Subanesthetic doses of ketamine to rats and monkeys rapidly increases radioligand binding in brain to phosphodiesterase-4, an indirect marker of cAMP
C](S)-rolipram, which has no specific binding to PDE4, was used to control for the effects of ketamine on blood flow and radioligand delivery in rats, no consistent effects were observed for ketamine. Collectively, the results suggest that ketamine infusion rapidly increases cAMP activity and may be an underlying mechanism for ketamine's rapid antidepressant effects. These data support a common pathway for cAMP and antidepressant action and suggest that PDE4 inhibition, particularly PDE4B, may be an effective and rapid-acting antidepressant mechanism.
Authors
- Susovan Jana (ORCID: https://orcid.org/0000-0001-9910-347X)
- Shawn Wu
- Cheryl L. Morse (ORCID: https://orcid.org/0000-0001-6213-3560)
- Sami S. Zoghbi (ORCID: https://orcid.org/0000-0001-5613-8314)
- Victor W. Pike (ORCID: https://orcid.org/0000-0001-9032-2553)
- Ioline D. Henter (ORCID: https://orcid.org/0000-0002-2379-2413)
- Raven Cureton
- Amanda Bardhoshi
- Matilah Pamie-George
- Robert B. Innis
- Jeih-San Liow
- Adrian E. Jenson
- Julia Totis (ORCID: https://orcid.org/0009-0003-9111-0546)
- Paul A. Parcon (ORCID: https://orcid.org/0000-0002-3606-3041)
- Amanda Olsen-Dufour
Institutions
- National Institutes of Health (US)
- National Institute of Mental Health (US)
Publication Details
- Journal
- Translational Psychiatry
- Published
- 2026-04-21
- DOI
- https://doi.org/10.1038/s41398-026-04039-w
- Primary Topic
- Phosphodiesterase function and regulation
- Type
- article
- Field-Weighted Citation Impact
- 0.00
Funders
- National Institute of Mental Health