J. Silvestre, Andrés G. Fernández, J. Palacios
Sep 1, 1999
Citations
5
Influential Citations
36
Citations
Quality indicators
Journal
Pharmacology Biochemistry and Behavior
Abstract
Rolipram is a specific cAMP phosphodiesterase type 4 (PDE4) inhibitor in the brain, which induces an increase in the intracellular levels of cAMP. Rolipram produces characteristic alterations in animal behavior, which have been suggested to be mediated mainly through an intracellular mechanism involving an increase in cAMP. However, specific mechanisms mediating the sedative effects of this compound have not yet been investigated. Because several lines of evidence indicate that the acetylcholine neural system may be involved in some effects of PDE4 inhibitors, the aim of this study was to elucidate whether the neurotransmitter acetylcholine is involved in the sedative effects induced by rolipram. The present study assessed the motor effects of rolipram in an exploratory behavioral test, the open field, in Wistar rats. The results show that rolipram (0.1-3.0 mg/kg SC) induced potent and dose-dependent hypoactivity, decreasing both locomotion and rearing. Physostigmine (0.03-0.3 mg/kg SC) potentiated a subeffective dose of rolipram (0.03 mg/kg SC), resulting in strong sedation, similar to that following higher doses of either rolipram or physostigmine alone, whereas the reduction in locomotor activity induced by rolipram (0.3 mg/kg SC) was completely reversed by scopolamine (0.03-0.3 mg/kg SC). These data provide preliminary evidence suggesting the involvement of the acetylcholinergic system in the sedative effects of rolipram.