SEROTONIN AGONISTS MIMIC THE PHASE-SHIFTING EFFECTS OF LIGHT ON THE MELATONIN RHYTHM IN RATS

The effect of serotonin agonists on the rhythmic excretion of the mela tonin metabolite 6-sulphatoxymelatonin was examined in rats. The anima ls were maintained in 12L:12D and administered saline, quipazine (10 m g/kg), ropylamino-8-hydroxy-1.2.3.4-tetrahydronaphthalene hydrobromide (8-OH-DPAT, 5 mg/kg) or buspirone (10 mg/kg), 4 h after dark (ZT16). All three drugs caused an acute, transient suppression of 6-sulphatoxy melatonin excretion and a significant delay (P < 0.01) in the onset of the nocturnal rise on the following night of 2.1 +/- 0.6, 1.4 +/- 0.7 and 1.5 +/- 0.3 h respectively while saline administration had no eff ect (0.4 +/- 0.2 h delay, P > 0.01). To examine the effects of the tim e of day of agonist administration, groups of rats were treated with q uipazine (10 mg/kg) or 8-OH-DPAT (5 mg/kg) 18, 24 or 30 h after the in itiation of continuous darkness (CT6, CT12 or CT18) and monitored for a further two nights. Quipazine but not 8-OH-DPAT injection at CT6 res ulted in a small but significant delay in the onset of 6-sulphatoxymel atonin excretion on the following night (1.0 +/- 0.2 h and 0.3 +/- 0.2 h), while treatment with both agonists at CT12 failed to affect the o nset of excretion (0.8 +/- 0.2 and 0.1 +/- 0.2 h). When quipazine (10 mg/kg) was administered at CT18, 6-sulphatoxymelatonin excretion was a cutely suppressed for the rest of the night and there was a large sign ificant delay in the onset of 6-sulphatoxymelatonin excretion (1.2 +/- 0.2 h) while a smaller delay was observed following 8-OH-DPAT adminis tration (0.8 +/- 0.2 h). The acute suppression of 6-sulphatoxymelatoni n excretion and subsequent phase delay following quipazine treatment a t CT18 was also evident at doses of 1 mg/kg (1.6 +/- 0.4 h) and 3 mg/k g (1.5 +/- 0.6 h). These results show that peripheral administration o f serotonin agonists active at 5HT(1a)/5HT(7) receptors mimic the dual effects of light on melatonin production in the rat and raise the pos sibility that serotonin pathways are more important in mediating the e ffects of retinally perceived light in the rat than previously believe d.