QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) All Versions of this Article: jpet.103.053215v1 307/1/246    most recent Submit a response Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Zhao, Y. Articles by O'Donnell, J. M. Search for Related Content PubMed PubMed Citation Articles by Zhao, Y. Articles by O'Donnell, J. M.

NEUROPHARMACOLOGY

Antidepressant-Induced Increase in High-Affinity Rolipram Binding Sites in Rat Brain: Dependence on Noradrenergic and Serotonergic Function

Department of Pharmacology, the University of Tennessee Health Science Center, Memphis, Tennessee

The effects of antidepressant treatment on the high- and low-affinity rolipram binding sites on type 4 phosphodiesterase (PDE4) were determined; previous work had shown that repeated antidepressant treatment increases the overall expression of PDE4. Rats were administered different doses of the antidepressant drugs desipramine or fluoxetine, or saline, for 1, 7, or 14 days. [³H]Rolipram and [³H]piclamilast were used to assess the high-affinity rolipram binding sites (HARBS) and low-affinity rolipram binding sites (LARBS) on PDE4 in the hippocampus and cerebral cortex. Repeated, but not acute, treatment with the antidepressants increased [³H]rolipram binding to membrane fractions in a dose-dependent manner; the HARBS component of [³H]piclamilast binding also was increased by these treatments. By contrast, the LARBS component of [³H]piclamilast binding was not altered. [³H]Rolipram and [³H]piclamilast binding to the cytosolic fractions of rat cerebral cortex and hippocampus was not altered by the antidepressant treatments. 6-Hydroxydopamine (6-OHDA; 300 µg i.c.v.) and 5,7-dihydroxytryptamine (5,7-DHT; 200 µg i.c.v.) were used to lesion noradrenergic and serotonergic neurons, respectively. The effects of desipramine, but not fluoxetine, on [³H]rolipram and [³H]piclamilast binding to rat hippocampal membranes were blocked by the 6-OHDA-induced lesion. By contrast, the effects of fluoxetine, but not desipramine, were reduced by the 5,7-DHT-induced lesion. This indicates that the up-regulation of the HARBS by desipramine and fluoxetine requires the integrity of noradrenergic and serotonergic neurons, respectively. Collectively, these results suggest that antidepressants, although acting through different pathways, may eventually lead to the regulation of components of the cAMP signal transduction system.

Address correspondence to: James M. O'Donnell, Ph.D., Department of Pharmacology, University of Tennessee Health Science Center, 874 Union Ave., Memphis, TN 38163. E-mail: jodonnell{at}utmem.edu

This article has been cited by other articles:

				M. A. Blount, R. Zoraghi, E. P. Bessay, A. Beasley, S. H. Francis, and J. D. Corbin Conversion of Phosphodiesterase-5 (PDE5) Catalytic Site to Higher Affinity by PDE5 Inhibitors J. Pharmacol. Exp. Ther., November 1, 2007; 323(2): 730 - 737. [Abstract] [Full Text] [PDF]

				X. Lu, A. M. Barr, J. W. Kinney, P. Sanna, B. Conti, M. M. Behrens, and T. Bartfai A role for galanin in antidepressant actions with a focus on the dorsal raphe nucleus PNAS, January 18, 2005; 102(3): 874 - 879. [Abstract] [Full Text] [PDF]