RT Journal Article SR Electronic T1 Antidepressant-like effects of rolipram and other inhibitors of cyclic adenosine monophosphate phosphodiesterase on behavior maintained by differential reinforcement of low response rate. JF Journal of Pharmacology and Experimental Therapeutics JO J Pharmacol Exp Ther FD American Society for Pharmacology and Experimental Therapeutics SP 1168 OP 1178 VO 264 IS 3 A1 J M O'Donnell YR 1993 UL http://jpet.aspetjournals.org/content/264/3/1168.abstract AB Four inhibitors of cyclic AMP phosphodiesterase (PDE), rolipram, Ro 20-1724, ICI 63,197 and CP 76,593, reduced response rates and increased reinforcement rates of rats under a differential reinforcement of low rate 72-sec schedule for water reinforcement in a dose-dependent manner. These actions of the PDE inhibitors are similar to those reported for proven antidepressant drugs. Administration of forskolin, which increases cyclic AMP levels by activation of the catalytic subunit of adenylyl cyclase, either i.p. or i.c.v. did not mimic the effects of the PDE inhibitors. The behavioral effects of the PDE inhibitors were not antagonized by the beta adrenergic antagonist propranolol, suggesting that these drugs were not altering behavior via an increase in norepinephrine release and an indirect stimulation of beta adrenergic receptors. 6-Hydroxydopamine-induced lesions of noradrenergic neurons increased sensitivity to rolipram. This suggests that alterations in PDE activity with a concomitant increase in sensitivity to PDE inhibitors may occur subsequent to functional denervation.