Behavior-dependent modulation of hippocampal EEG activity by the selective norepinephrine reuptake inhibitor reboxetine in rats

Abstract

Both active wakefulness and rapid eye movement sleep (REM) give rise to rhythmic synchronized hippocampal field oscillations, known as theta activity. Antidepressant drugs, including norepinephrine re-uptake inhibitors are proven to diminish REM sleep, and REM sleep-related hippocampal theta oscillation. Since reboxetine, a highly selective norepinephrine re-uptake inhibitor has been shown to block REM sleep, but induce or facilitate hippocampal theta activity in anesthetized rats, the current study investigated the effects of reboxetine on stage- and behavior dependent theta activity. Polysomnographic recordings, which included hippocampal field potentials at the hippocampal fissure, were carried out in rats for 8 h during the light phase of the circadian cycle. Theta rhythm was analyzed during three different behavioral conditions: REM sleep, during motor activity in a familiar environment, and during exploration in a novel environment. We found that, compared with REM sleep, theta power was relatively low during periods of active wakefulness when the animal was in the familiar home cage, but considerably increased during exploration in a novel environment. Reboxetine suppressed sleep and thus abolished REM sleep-related hippocampal theta rhythm, attenuated theta in the familiar environment, and significantly enhanced theta oscillations associated with exploratory behavior. Our findings demonstrate a state- and behavior-dependent modulation of hippocampal theta activity by reboxetine, providing further evidence for a prominent role of norepinephrine in arousal and focused or selective attention.