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.