Effect of Rolipram, a Phosphodiesterase Inhibitor and Potential Antidepressant, on the Firing Rate of Central Monoaminergic Neurons in the Rat

Rolipram is a potent phosphodiesterase inhibitor, active in classical pharmacological tests used in the screening of antidepressants (AD). In contrast with classical AD, rolipram does not block the reuptake of monoamines, but its action on the metabolic degradation of cyclic AMP may enhance adenylate-cyclase linked catecholaminergic and serotonergic transmission. Biochemical studies showed that rolipram induces various modifications in the turnover of monoamines but the net effect of these modifications on the electrical activity of monoaminergic neurons remained to be elucidated. Thus, the influence of rolipram on the firing rate of central locus coeruleus (LC) noradrenergic neurons, mesolimbic (A10) dopaminergic neurons and dorsal raphe (DR) serotonergic neurons was investigated. When rolipram was perfused into the jugular vein, it produced a long-lasting excitatory effect on LC neurons, a prolonged but usually partial inhibitory effect on A10 neurons and no consistent effect on DR neurons. The action of rolipram on monoaminergic neurons contrasts with that of most classical and new AD in which the electrical activity of LC and/or DR neurons decreases.