@article {Markus525, author = {Regina P. Markus and Jussara M. Santos and Wagner Zago and L{\i}́via A. C. Ren{\'o}}, title = {Melatonin Nocturnal Surge Modulates Nicotinic Receptors and Nicotine-Induced [3H]Glutamate Release in Rat Cerebellum Slices}, volume = {305}, number = {2}, pages = {525--530}, year = {2003}, doi = {10.1124/jpet.102.045625}, publisher = {American Society for Pharmacology and Experimental Therapeutics}, abstract = {In mammals, the most important synchronizer for endogenous rhythms is the environmental light/dark cycle. In this report we have explored the ability of light/dark cycle and melatonin, the pineal hormone released during the night, to modulate cerebellar cholinergic input by interfering with the nicotinic acetylcholine receptors{\textquoteright} (nAChRs) availability. Through the analysis of the response to selective cholinergic agonists and antagonists, we observed that nAChRs containing the α7 gene product mediate the release of [3H]glutamate from rat cerebellum slices. The [3H]glutamate overflow induced by α7 nAChR activation was higher during the dark phase, although the number of α-[125I]bungarotoxin binding sites, but not the [3H]nicotine binding sites (Bmax), was reduced. On the other hand, glutamate-evoked [3H]glutamate release was not modified by the hour of the day. Finally, we show that the nocturnal increase in nicotine-evoked [3H]glutamate release is imposed by a nocturnal surge of melatonin, as it is abolished when pineal melatonin production is inhibited by either maintaining the animals in constant light for 48 h or by injecting propranolol just before lights off for 2 days. The difference between light and dark [3H]glutamate-evoked release is restored in propranolol-treated animals that received melatonin during the dark period. In conclusion, we show that nicotine-evoked [3H]glutamate release in rat cerebellum presents a diurnal variation, driven by nocturnal pineal melatonin surge. The American Society for Pharmacology and Experimental Therapeutics}, issn = {0022-3565}, URL = {https://jpet.aspetjournals.org/content/305/2/525}, eprint = {https://jpet.aspetjournals.org/content/305/2/525.full.pdf}, journal = {Journal of Pharmacology and Experimental Therapeutics} }