title: Differential effect of cannabinoid agonists and endocannabinoids on histamine release from distinct regions of the rat brain.
abstract: Cannabinoids exert complex actions on neurotransmitter systems involved in cognition, locomotion, appetite, but no information was available so far on the interactions between the endocannabinoid system and histaminergic neurons that command several, similar behavioural states and memory. In this study, we investigated the effect of cannabimimetic compounds on histamine release using the microdialysis technique in the brain of freely moving rats. We found that systemic administration of the cannabinoid receptors 1 (CB1-r) agonist arachidonyl-2'chloroethylamide/N-(2chloroethyl)-5Z,8Z,11Z,14Z-eicosatetraenamide (ACEA; 3 mg/kg) increased histamine release from the posterior hypothalamus, where the histaminergic tuberomamillary nuclei (TMN) are located. Local infusions of ACEA (150 nm) or R(+)-methanandamide (mAEA; 1 microm), another CB1-r agonist, in the TMN augmented histamine release from the TMN, as well as from two histaminergic projection areas, the nucleus basalis magnocellularis and the dorsal striatum. When the endocannabinoid uptake inhibitor AM404 was infused into the TMN, however, increased histamine release was observed only in the TMN. The cannabinoid-induced effects on histamine release were blocked by co-administrations with the CB1-r antagonist AM251. Using double-immunofluorescence labelling and confocal laser-scanning microscopy, CB1-r immunostaining was found in the hypothalamus, but was not localized onto histaminergic cells. The modulatory effect of cannabimimetic compounds on histamine release apparently did not involve inhibition of gamma-aminobutyric acid (GABA)ergic neurotransmission, which provides the main inhibitory input to the histaminergic neurons in the hypothalamus, as local infusions of ACEA did not modify GABA release from the TMN. These profound effects of cannabinoids on histaminergic neurotransmission may partially underlie some of the behavioural changes observed following exposure to cannabinoid-based drugs.
authors.affiliation: Dipartimento di Farmacologia Preclinica e Clinica, Viale Pieraccini 6, 50139 Firenze, Italy.
authors.forename: Gabriele
authors.initials: G
authors.lastname: Cenni
authors.forename: Patrizio
authors.initials: P
authors.lastname: Blandina
authors.forename: Ken
authors.initials: K
authors.lastname: Mackie
authors.forename: Daniele
authors.initials: D
authors.lastname: Nosi
authors.forename: Lucia
authors.initials: L
authors.lastname: Formigli
authors.forename: Patrizia
authors.initials: P
authors.lastname: Giannoni
authors.forename: Chiara
authors.initials: C
authors.lastname: Ballini
authors.forename: Laura
authors.initials: L
authors.lastname: Della Corte
authors.forename: Pier Francesco
authors.initials: PF
authors.lastname: Mannaioni
authors.forename: M Beatrice
authors.initials: MB
authors.lastname: Passani
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D001095:Arachidonic Acids / Q000494:pharmacology*; D001640:Bicuculline / Q000494:pharmacology; D063385:Cannabinoid Receptor Modulators / Q000494:pharmacology*; D002186:Cannabinoids / Q000819:agonists*; D002454:Cell Differentiation / Q000187:drug effects* / Q000502:physiology; D002851:Chromatography, High Pressure Liquid / Q000379:methods; D063388:Endocannabinoids; D018756:GABA Antagonists / Q000494:pharmacology; D006632:Histamine / Q000378:metabolism*; D007031:Hypothalamus / Q000187:drug effects*; D007150:Immunohistochemistry / Q000379:methods; D008297:Male; D017551:Microdialysis / Q000379:methods; D010880:Piperidines / Q000494:pharmacology; D011720:Pyrazoles / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D043884:Receptor, Cannabinoid, CB1 / Q000378:metabolism; D013997:Time Factors; D014851:Wakefulness; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
chemical_list: D001095:Arachidonic Acids; D063385:Cannabinoid Receptor Modulators; D002186:Cannabinoids; D063388:Endocannabinoids; D018756:GABA Antagonists; D010880:Piperidines; D011720:Pyrazoles; D043884:Receptor, Cannabinoid, CB1; C119325:arachidonyl-2-chloroethylamide; C103505:AM 251; D005680:gamma-Aminobutyric Acid; D006632:Histamine; C107594:N-(4-hydroxyphenyl)arachidonylamide; D001640:Bicuculline