MODULATION OF LIGHT-INDUCED C-FOS EXPRESSION IN THE SUPRACHIASMATIC NUCLEI BY 5-HT1A RECEPTOR AGONISTS

In previous studies, we showed that light-induced Fos protein expressi on in the ventrolateral SCN is markedly inhibited by the nonselective serotonergic, quipazine. The present experiments were undertaken to ch aracterize the effects of various serotonin (5-HT) receptor ligands on photic signalling in the SCN. The extent of expression of light-induc ed Fos-like immunoreactivity (Fos-LI) in the SCN was used as a marker for this response. Exposure of hamsters to a light pulse delivered dur ing the latter part of the dark phase (7 h after lights-off; LD 14:10) elicited an intense expression of Fos-LI in nuclei of cells situated principally in the ventrolateral region of the SCN. Pretreatment with an i.p. injection of the 5-HT1A receptor agonists, 8-OH-DPAT or buspir one, 30 min before the light pulse significantly inhibited the photic expression of Fos-LI (maximal suppression 45.7 +/- 8.1 and 43.0 +/- 1. 3%, respectively, both P < 0.01 vs. vehicle controls). Treatment with the 5-HT1A receptor antagonist, NAN-190, administered 15 min before 8- OH-DPAT injection prevented the inhibitory effect of 8-OH-DPAT (100.9 +/- 6.0% vs. controls, P > 0.9). Pretreatment with the 5-HT1B receptor agonist, TFMPP, caused a small but significant suppression of Fos-LI (14.8 +/- 3.5% vs. controls, P < 0.05). In contrast to the significant 5-HT1 receptor agonist effects, pretreatment with 5-HT, or 5-HT3 rece ptor agonists, alpha-methyl-5-HT and 1-phenylbiguanide had little supp ressive effect on Fos-LI (7.9 +/- 2.1 and 13.0 +/- 5.0% suppression, r espectively, both P > 0.1 vs. controls). In animals receiving treatmen ts to raise the extracellular concentration of endogenous 5-HT, includ ing pretreatment with L-tryptophan alone or in combination with the 5- HT releaser, fenfluramine, and the type A monoamine oxidase inhibitor, harmaline, light-induced Fos-LI was reduced by 33.8 +/- 4.5 and 53.2 +/- 4.8%, respectively (P < 0.05). Together, these findings support a role for 5-HT in regulating photic signal transduction in the SCN and suggest that this is mediated principally by 5-HT1A receptors. Moreove r, the finding that light-induced Fos-LI in the SCN is inhibited by L- tryptophan raises the possibility that dietary tryptophan could modula te the entraining effect of light on pacemaker activity.