Acute and chronic escitalopram alter EEG gamma oscillations differently: relevance to therapeutic effects.

Abstract

Brain oscillations in the gamma frequency band of the electroencephalogram (EEG) have been implicated in several sensory and cognitive processes, and have also been associated with numerous neuropsychiatric disorders, including depression. The widely prescribed selective serotonin reuptake inhibitors (SSRIs), similarly to other antidepressants, are known to produce markedly different effects on sleep and behavioral measures with acute and chronic administration. Although there are studies examining the acute effect of escitalopram on slower (<30Hz) oscillations, we hardly could find any data about the effect of the drug on higher-frequency EEG oscillations (>30Hz) in different sleep-wake stages, particularly comparing the acute and chronic effects of the drug concerning gamma oscillations. Our aim was to investigate, how escitalopram affects gamma power in different sleep-wake stages, and to discover possible differential effects between acute and chronic treatment. EEG-equipped Wistar rats were treated with escitalopram or vehicle acutely (10mg/kg, i.p.) or chronically (10mg/kg/day for 21days, osmotic minipumps) and frontoparietal EEG, electromyogram and motor activity were recorded during the first 3h of passive phase. We found that acute and chronic escitalopram treatment affected gamma oscillations differently. While acute escitalopram caused a reduction in gamma power during rapid eye movement sleep (REMS) and intermediate stage of sleep (IS), chronic treatment caused an elevation in gamma power during non-REMS stages, namely in light and deep slow-wave sleep (SWS-1 and SWS-2, respectively) and in IS. However, gamma activity during active and passive wakefulness (AW and PW, respectively) was not influenced by either acute or chronic dosing of escitalopram. Furthermore, we found that in drug-free (vehicle-treated) rats, a relatively high gamma power was present during wakefulness and REMS, while a much lower power was measured during non-REMS stages. These findings indicate that acute and chronic administration of escitalopram alter gamma activity differently, moreover, in a sleep-wake stage dependent manner that may be related to differential therapeutic and/or side effects.