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  • Title: Electrophysiological effects of fluoxetine and duloxetine in the dorsal raphe nucleus and hippocampus.
    Author: Smith JE, Lakoski JM.
    Journal: Eur J Pharmacol; 1997 Mar 26; 323(1):69-73. PubMed ID: 9105878.
    Abstract:
    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 nucleus and the hippocampus of chloral hydrate-anesthetized male rat. Systemic intravenous administration of duloxetine or fluoxetine inhibited dorsal raphe nucleus cell firing in a dose-dependent manner; duloxetine suppressed cell firing at significantly lower doses (ED100 1.4 +/- 0.3 mg/kg) than fluoxetine (ED100 10.0 +/- 2.0 mg/kg). In the hippocampus, microiontophoretic application of duloxetine or fluoxetine (0.01 M, pH 5.5; 5-40 nA) produced minimal inhibition of cell firing. When duloxetine was co-applied with 5-HT, the recovery response (RT50 values) of hippocampal pyramidal neurons to 5-HT application was not altered. In contrast, co-application of fluoxetine with 5-HT at the same iontophoretic currents significantly increased (59%) the RT50 values produced by 5-HT application alone. This physiological and pharmacological study contributes to understanding the cellular mechanisms of these agents which may be useful in the treatment of depression.
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