Antidepressant-like profile and reduced sensitivity to rolipram in mice deficient in the PDE4D phosphodiesterase enzyme
by
Zhang HT, Huang Y, Jin SL, Frith SA,
Suvarna N, Conti M, O'Donnell JM.
Department of Pharmacology,
University of Tennessee Health Science Center,
Memphis, TN 38163, USA.
hzng@utmem.edu
Neuropsychopharmacology. 2002 Oct;27(4):587-95

ABSTRACT

Pharmacological inhibition of type 4 cyclic adenosine monophosphate (cAMP)-specific phosphodiesterase (PDE4) produces antidepressant-like effects in animals; however, it is not known which of the four PDE4 subtypes mediates these actions. In the present study, immunoblot analysis showed loss of phosphodiesterase 4D (PDE4D) expression in the cerebral cortex and hippocampus of PDE4D knockout (PDE4D-/-) mice, but unchanged PDE4A and PDE4B expression, relative to the wild type (PDE4D+/+) and heterozygous knockout (PDE4D+/-) mice. This reduced expression was accompanied by a reduction in PDE4 activity, while non-PDE4 activity was unchanged. PDE4D-/- mice exhibited decreased immobility in tail-suspension and forced-swim tests, which is indicative of an antidepressant-like effect on behavior. Desipramine and fluoxetine produced similar antidepressant-like effects in all three genotypes, even though their behavioral baselines differed markedly. By contrast, the PDE4 inhibitor rolipram only produced antidepressant-like effects in PDE4D+/+ mice. Consistent with this, rolipram potentiated isoproterenol-induced cyclic AMP formation only in the PDE4D+/+ mice. These results suggest that PDE4D is an essential mediator of the antidepressant-like effects of rolipram, and that PDE4D-regulated cyclic adenosine monophosphate signaling may play a role in the pathophysiology and pharmacotherapy of depression.

Options
Rolipram
21st Century
Rolipram and memory
Rolipram plus imipramine
Rolipram and wakefulness
Rolipram and new brain cells
Phosphodiesterase inhibitors
Rolipram reduces excitotoxic neuronal damage
PDE4D inhibitor rolipram and glucocorticoid receptors
The antidepressant and anti-inflammatory effects of rolipram

Refs
and further reading

HOME
HedWeb
Nootropics
cocaine.wiki
Future Opioids
BLTC Research
MDMA/Ecstasy
Superhapiness?
Utopian Surgery?
The Abolitionist Project
The Hedonistic Imperative
The Reproductive Revolution
Critique of Huxley's Brave New World

The Good Drug Guide
The Responsible Parent's Guide
To Healthy Mood Boosters For All The Family