Preliminary evidence for an involvement of the cholinergic system in the sedative effects of rolipram in rats

Rolipram is a specific cAMP phosphodiesterase type 4 (PDE4) inhibitor in th e brain, which induces an increase in the intracellular levels of cAMP, Rol ipram produces characteristic alterations in animal behavior, which have be en suggested to be mediated mainly through an intracellular mechanism invol ving an increase in cAMP. However, specific mechanisms mediating the sedati ve effects of this compound have not yet been investigated. Because several lines of evidence indicate that the acetylcholine neural system may be inv olved in some effects of PDE4 inhibitors, the aim of this study was to eluc idate whether the neurotransmitter acetylcholine is involved in the sedativ e effects induced by rolipram. The present study assessed the motor effects of rolipram in an exploratory behavioral test, the open field, in Wistar r ats. The results show that rolipram (0.1-3.0 mg/kg SC) induced potent and d ose-dependent hypoactivity, decreasing both locomotion and rearing. Physost igmine (0.03-0.3 mg/kg SC) potentiated a subeffective dose of rolipram (0.0 3 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 revers ed by scopolamine (0.03-0.3 mg/kg SC). These data provide preliminary evide nce suggesting the involvement of the acetylcholinergic system in the sedat ive effects of rolipram. (C) 1999 Elsevier Science Inc.