Nicotinic enhancement of the noradrenergic inhibition of sleep-promoting neurons in the ventrolateral preoptic area
| Autor: | Benoît Saint-Mleux, Barbara E. Jones, Laurence Bayer, Emmanuel Eggermann, Danièle Machard, Arnaud Bisetti, Michel Muhlethaler, Mauro Serafin |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2004 |
| Předmět: |
Nicotinic Agonists/ pharmacology
Potassium Channels Patch-Clamp Techniques Receptors Nicotinic Norepinephrine/ metabolism Sleep/physiology Norepinephrine chemistry.chemical_compound Preoptic Area/anatomy & histology/cytology/ physiology Muscarinic acetylcholine receptor Nicotinic Agonists Cells Cultured Neurons Chemistry General Neuroscience Drug Synergism Neurons/drug effects/ physiology Muscarinic Antagonists/pharmacology Receptors Muscarinic Potassium Channels/metabolism Presynaptic Terminals/metabolism Nicotinic agonist Receptors Nicotinic/metabolism Epibatidine Brief Communications Acetylcholine medicine.drug Agonist medicine.drug_class Presynaptic Terminals Muscarinic Antagonists Muscarinic Agonists Inhibitory postsynaptic potential Receptors Muscarinic/metabolism medicine Animals Acetylcholine/ pharmacology Muscarinic Agonists/pharmacology Methyllycaconitine Electric Conductivity Neural Inhibition Preoptic Area ddc:616.8 Rats nervous system Cholinergic Sleep Neuroscience |
| Zdroj: | Journal of Neuroscience, Vol. 24, No 1 (2004) pp. 63-67 |
| ISSN: | 0270-6474 |
| Popis: | According to multiple lines of evidence, neurons in the ventrolateral preoptic area (VLPO) that contain GABA promote sleep by inhibiting neurons of the arousal systems. Reciprocally, transmitters used by these systems, including acetylcholine (ACh) and noradrenaline (NA), exert an inhibitory action on the VLPO neurons. Because nicotine, an agonist of ACh, acts as a potent stimulant, we queried whether it might participate in the cholinergic inhibition of these sleep-promoting cells. Indeed, we found that ACh inhibits the VLPO neurons through a nicotinic, as well as a muscarinic, action. As evident in the presence of atropine, the non-muscarinic component was mimicked by epibatidine, a nonselective nicotinic ACh receptor (nAChR) agonist and was blocked by dihydro-β-erythroidine, a nonselective nAChR antagonist. It was not, however, blocked by methyllycaconitine, a selective antagonist of the α7 subtype, indicating that the action was mediated by non-α7 nAChRs. The nicotinic inhibition was attributed to a presynaptic facilitation of NA release because it persisted in the presence of tetrodotoxin and was blocked by yohimbine and RS 79948, which are both selective antagonists of α2 adrenergic receptors. Sleep-promoting VLPO neurons are thus dually inhibited by ACh through a muscarinic postsynaptic action and a nicotinic presynaptic action on noradrenergic terminals. Such dual complementary actions allow ACh and nicotine to enhance wakefulness by inhibiting sleep-promoting systems while facilitating other wake-promoting systems. |
| Databáze: | OpenAIRE |
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