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' (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.
Footnotes
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Financial support: Fundação de Amparo àPesquisa do Estado de São Paulo (FAPESP, 00/00659-2). J.M.S., W.M.Z., and L.A.C.R. were graduate fellows from FAPESP; R.P.M. is a fellow of the Conselho Nacional de Ciência e Tecnologia. This work contains data from the thesis of J.S.M. and W.M.Z. The abstract was presented at the IXth European Pineal and Biological Rhythm Symposium, Aberdeen, Scotland, 18–21 July, 2002.
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DOI: 10.1124/jpet.102.045625
- Abbreviations:
- nAChR
- nicotinic acetylcholine receptor
- LL
- exposed to light only for 2 days
- MLA
- methyllycaconitine
- Received October 11, 2002.
- Accepted January 14, 2003.
- The American Society for Pharmacology and Experimental Therapeutics
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