Electrophysiological study of the effects of the reuptake inhibitor duloxetine on serotonergic responses in the aging hippocampus.
The pharmacological effects of the dual serotonin (5-hydroxy-tryptamine, 5-HT) and norepinephrine reuptake inhibitor, duloxetine, on serotonergic function in the aging hippocampus were studied using an in vivo chloral hydrate-anesthetized preparation in the female Fischer 344 rate across the life-span (3-8, 11-14, 18-22 and 24-27 months). Within each age group, duloxetine co-application did not alter the inhibitory responses (IT50 values) produced by the application of 5-HT alone. With continuous co-application of duloxetine (> or = 5 min), the recovery time (RT50 values) following 5-HT application did not change in the youngest ages, whereas in the 24- to 27-month-old group a significant increase in the time to recovery of baseline firing was found with co-application of duloxetine (68%; p < 0.05), followed by a return to baseline levels. These results contribute to identification of cellular mechanisms of duloxetine which may underlie its action as an antidepressant in the elderly.
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
D000200:Action Potentials / Q000187:drug effects*; D000375:Aging / Q000502:physiology*; D000818:Animals; D018687:Antidepressive Agents, Second-Generation / Q000494:pharmacology*; D003891:Desipramine / Q000494:pharmacology; D000068736:Duloxetine Hydrochloride; D005260:Female; D006624:Hippocampus / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D007478:Iontophoresis; D051381:Rats; D011916:Rats, Inbred F344; D017367:Selective Serotonin Reuptake Inhibitors / Q000494:pharmacology*; D013876:Thiophenes / Q000494:pharmacology*
D018687:Antidepressive Agents, Second-Generation; D003891:Desipramine; D000068736:Duloxetine Hydrochloride; D017367:Selective Serotonin Reuptake Inhibitors; D013876:Thiophenes