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 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.
Smith
J E
JE
Department of Pharmacology, Milton S. Hershey Medical Center, Pennsylvania State University College of Medicine, Hershey 17033, USA.
Lakoski
J M
JM
D000704:Analysis of Variance; D000818:Animals; D004305:Dose-Response Relationship, Drug; D000068736:Duloxetine Hydrochloride; D004594:Electrophysiology; D005473:Fluoxetine / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D006624:Hippocampus / Q000166:cytology / Q000187:drug effects*; D007262:Infusions, Intravenous; D007478:Iontophoresis; D008297:Male; D009474:Neurons / Q000166:cytology / Q000187:drug effects; D011903:Raphe Nuclei / Q000166:cytology / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011985:Receptors, Serotonin / Q000187:drug effects* / Q000378:metabolism; D044263:Receptors, Serotonin, 5-HT1; D017367:Selective Serotonin Reuptake Inhibitors / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D013876:Thiophenes / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use
D000068736:Duloxetine Hydrochloride; D005473:Fluoxetine; D011985:Receptors, Serotonin; D044263:Receptors, Serotonin, 5-HT1; D017367:Selective Serotonin Reuptake Inhibitors; D013876:Thiophenes