ELECTROPHYSIOLOGICAL EFFECTS OF FLUOXETINE AND DULOXETINE IN THE DORSAL RAPHE NUCLEUS AND HIPPOCAMPUS

The cellular electrophysiological effects of duloxetine (LY248686), a dual serotonin (5-hydroxytryptamine, 5-HT) and norepinephrine reuptake inhibitor, and the selective serotonin reuptake inhibitor fluoxetine were compared on spontaneously active neurons in the dorsal raphe nucl eus and the hippocampus of chloral hydrate-anesthetized male rat. Syst emic intravenous administration of duloxetine or fluoxetine inhibited dorsal raphe nucleus cell firing in a dose-dependent manner; duloxetin e suppressed cell firing at significantly lower doses (ED(100) 1.4 +/- 0.3 mg/kg) than fluoxetine (ED(100) 10.0 +/- 2.0 mg/kg). In the hippo campus, microiontophoretic application of duloxetine or fluoxetine (0. 01 M, pH 5.5; 5-40 nA) produced minimal inhibition of cell firing. Whe n duloxetine was co-applied with 5-HT, the recovery response (RT(50) v alues) of hippocampal pyramidal neurons to 5-HT application was not al tered. In contrast, co-application of fluoxetine with 5-HT at the same iontophoretic currents significantly increased (59%) the RT(50) value s produced by a 5-HT application alone. This physiological and pharmac ological study contributes to understanding the cellular mechanisms of these agents which may be useful in the treatment of depression. (C) 1997 Elsevier Science B.V.