Greater effects of fluoxetine and its combination with (-)-pindolol in elevating hypothalamic serotonin in rats...

Administration of fluoxetine (10 mg/kg i.p.) caused a significantly greater increase in extracellular 5-HT levels in hypothalamus of rats adapted to a reverse light period (lights off 9:00 am-9:00 pm) than those adapted to the regular cycle (lights off 6:00 pm-6:00 am). Sequential administration of the antagonist 5-HT1A/beta-adrenergic receptors (-)-pindolol at 0.1, 0.3, 1, and 3 mg/kg s.c. significantly enhanced the fluoxetine-induced elevation of 5-HT levels in both groups of rats. (-)-Pindolol at 0.1 mg/kg potentiated the fluoxetine-induced elevation in 5-HT levels significantly higher in rats adapted to the reverse light cycle than in those accustomed to the regular light cycle. The greater effects of fluoxetine and the subsequent administration of (-)-pindolol in the reverse cycle group may relate to the difference in activity of 5-HT neurons in the dorsal raphe of conscious animals adapted to the two light periods.