Neuroscience Letters, 127 (1991) 9 12 © 1991 Elsevier Scientific Publishers Ireland Ltd. 0304-3940/91/$ 03.50 ADONIS 0304394091002565 NSL 07772 Photic induction of Fos protein in the suprachiasmatic nucleus is inhibited by the NMDA receptor antagonist MK-801 Hiroshi Abe l, Benjamin Rusak 1,3 and Harold A. Robertson 2 Departments of 1Psychology and 2Pharmacology, Dalhousie University, Halifax, N.S. (Canada) and 3Department of Biomedical Sciences, Faculty of Health Sciences, McMaster University, Hamilton, Ont. (Canada) (Received 15 January 1991; Revised version received 22 February 1991; Accepted 27 February 199 I) Key words: Suprachiasmatic nucleus; c-fos; MK-801; NMDA receptor; Hamster; Circadian rhythm Exposure of rodents to light can induce expression of a number of immediate-early genes, including c-fos, in cells of the suprachiasmatic nucleus (SCN), a dominant pacemaker in the mammalian circadian system. We examined the effects of pre-treatment with the non-competitive N-methyl-D- aspartate (NMDA) receptor antagonist MK-801, on the induction of Fos-like immunoreactivity (Fos-lir) in cells in the hamster SCN. At doses of 3 and 5 mg/kg, MK-801 treatment blocked photic induction of Fos-lir in the rostral SCN and ventrolateral portions of the caudal SCN but failed to block induction of Fos-lir in a discrete region of the dorsolateral SCN. These results suggest that photic induction of Fos-lir in most of the SCN depends on activation of an NMDA-type receptor which is sensitive to MK-801, but that Fos-lir in one portion of the SCN is induced by a mechanism which is not antagonized by MK-801. The suprachiasmatic nucleus (SCN) of the anterior hypothalamus is a dominant pacemaker in the mamma- lian circadian system and is involved in both the gene- ration and synchronization (entrainment) of many daily rhythms [17]. Entrainment of rhythms by lighting cycles results from shifts of the internally generated rhythm in response to photic input near the dawn and dusk transi- tions. Two pathways convey photic information relevant to entrainment to the SCN: a monosynaptic projection from retinal ganglion cells (retinohypothalamic tract, RHT) [15] and an indirect projection via the intergenicu- late leaflet (IGL) and ventral lateral geniculate nucleus (vLGN) (geniculohypothalamic tract, GHT) [5]. Neuropharmacological and neurophysiological stud- ies have suggested a role for excitatory amino acids (EAAs), such as L-glutamate and L-aspartate, in mediat- ing photic input to the SCN [1, 12, 20]. Recent reports indicate that light-induced phase shifts of activity rhythms in hamsters are blocked by systemic injections of MK-801 [(+)-5-methyl- 10,11-dihydro-5H-diben- zo[a,d]cyclohepten-5,10-imine maleate] which is a non- competitive antagonist of the N-methyl-D-aspartate (NMDA) subtype of excitatory amino acid receptors [2]. In addition, NMDA application causes sustained, dose- dependent activation of SCN cells in hypothalamic slice Correspondence." H. Abe, Department of Psychology, Life Sciences Centre, Dalhousie University, Halifax, N.S. Canada B3H 4J 1. preparations, and NMDA antagonists can block re- sponses of SCN neurons to electrical stimulation of the chiasm [11]. These studies suggest that NMDA receptors are involved in transmitting photic information to the SCN-based pacemaker. Retinal illumination also induces expression of vari- ous immediate-early genes, including c-fos, z/f-268 (NGFI-A) and several members of thejun family, in cells in the retinorecipient zones of the SCN and in geniculate areas that give rise to the GHT [16, 18; Rusak et al., unpublished observations]. There is also a strong circa- dian modulation of induction, which occurs primarily or exclusively in response to light given during the night, the circadian phase at which light can shift rhythms [10, 18], suggesting a connection to photic entrainment mechanisms. Since NMDA receptors appear to play a role in mediating photic effects on the SCN, and since MK-801 can block c-fos induction in other brain regions [3, 6], we examined whether blockade of the NMDA receptor with MK-801 can prevent photic induction of Fos-like immunoreactivity (Fos-lir) in hamster SCN cells. Adult, male Syrian hamsters (LVG:lak) were housed singly in cages enclosed in individual, light-tight boxes under a daily lighting cycle with 14 h of light (L), provid- ed by a General Electric Cool White fluorescent tube (~ 30 lux), alternating with 10 h of total darkness (D). Animals were injected i.p. 4-5 h into the daily D phase