Anandamide centrally depresses the respiratory rhythm generator of neonatal mice.
Endogenous cannabinoid receptors are widely distributed throughout the CNS, including the brainstem, and modulate a variety of functions, including breathing. In adult rats, activation of cannabinoid 1 receptors has been shown to depress breathing. Here in neonatal mice, we used in vitro electrophysiology, pharmacology, and immunohistochemistry to analyse the central effects of the endocannabinoid anandamide (AEA) on the activity of the medullary respiratory rhythm generator (RRG). First of all, in vitro electrophysiology on medullary preparations has revealed that bath application of AEA (30 μM, 15 min) significantly depressed respiratory activity. Secondly, applying pre-treatments with alpha-1 (Prazosin, 5 μM, 10 min) and alpha-2 (Yohimbine, 5 μM, 10 min) adrenoceptor antagonists prior to AEA application abolished the AEA-induced depression of the RRG. Finally, immunostaining revealed a dense network of fibres positive for the cannabinoid 1 receptor in the ventrolateral medulla (VLM), a region known to contain both the RRG and the modulatory A1/C1 catecholaminergic group. Moreover, cannabinoid 1 receptor positive fibres were found in close apposition with A1/C1 catecholaminergic cells, identified by the presence of tyrosine hydroxylase. In regard of our electrophysiological, pharmacological and immunostaining results, we conclude that AEA has a central depressive effect on the neonatal RRG, probably via the medullary A1/C1 catecholaminergic neurons which are already known to modulate the respiratory rhythm generator.
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Centre de Recherche en Neurobiologie-Neurophysiologie de Marseille CRN2M, Département de Physiologie Neurovégétative (PNV), Université Paul Cézanne Aix Marseille III, Faculté des Sciences et Techniques St. Jérôme, UMR, 6231 CNRS, Marseille, France.
Caravagna
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Hilaire
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Peyronnet
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Cayetanot
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D058668:Adrenergic alpha-1 Receptor Antagonists / Q000494:pharmacology; D058669:Adrenergic alpha-2 Receptor Antagonists / Q000494:pharmacology; D000818:Animals; D000831:Animals, Newborn; D001095:Arachidonic Acids / Q000494:pharmacology / Q000502:physiology*; D063385:Cannabinoid Receptor Modulators / Q000494:pharmacology / Q000502:physiology*; D063388:Endocannabinoids; D066298:In Vitro Techniques; D008526:Medulla Oblongata / Q000187:drug effects / Q000502:physiology; D051379:Mice; D010507:Periodicity; D053284:Polyunsaturated Alkamides / Q000494:pharmacology; D011224:Prazosin / Q000494:pharmacology; D043884:Receptor, Cannabinoid, CB1 / Q000378:metabolism; D018340:Receptors, Adrenergic, alpha-1 / Q000502:physiology; D018341:Receptors, Adrenergic, alpha-2 / Q000502:physiology; D012125:Respiratory Center / Q000187:drug effects / Q000502:physiology*; D015016:Yohimbine / Q000494:pharmacology
D058668:Adrenergic alpha-1 Receptor Antagonists; D058669:Adrenergic alpha-2 Receptor Antagonists; D001095:Arachidonic Acids; D063385:Cannabinoid Receptor Modulators; D063388:Endocannabinoids; D053284:Polyunsaturated Alkamides; D043884:Receptor, Cannabinoid, CB1; D018340:Receptors, Adrenergic, alpha-1; D018341:Receptors, Adrenergic, alpha-2; D015016:Yohimbine; C078814:anandamide; D011224:Prazosin