Fluoxetine Modulates the Circadian Biological Clock via Phase Advances of Suprachiasmatic Nucleus Neuronal Firing

The documented ability of serotonin (5-HT) to directly modulate circadian rhythms prompted interest in a similar role for therapeutic agents that readily enhance 5-HT neurotransmission, namely the selective serotonin reuptake inhibitors (SSRIs). Extracellular recordings of unit firing of suprachiasmatic nucleus (SCN) neurons maintained in slice culture enabled determinations of circadian rhythmicity. Shifts in the peak of activity were determined during the next circadian cycle following drug exposure. Fluoxetine (10 μm, 60 minutes incubation) produced robust phase advances only in the presence of L-tryptophan (.5 μm), added to maintain serotonergic tone. Actions of SSRIs at the level of the circadian biological clock add to the list of pharmacological effects for this drug class and encourage speculation as to their importance clinically.