S18616, a highly potent spiroimidazoline agonist at alpha(2)-adrenoceptors: II. Influence on monoaminergic transmission, motor function, and anxiety in comparison with dexmedetomidine and clonidine.

摘要: The α2-adrenoceptor (AR) agonist, S18616 {( S )-spiro[(1-oxa-2-amino-3-azacyclopent-2-ene)-4,2′-(8′-chloro-1′,2′,3′,4′-tetrahydronaphthalene)] accompanying article}, suppressed electrical activity of adrenergic neurons in the locus ceruleus, an action reversed by α2-AR antagonist, idazoxan, which itself enhanced their firing rate. Electrical serotonergic dorsal raphe nucleus was similarly suppressed, likewise blocked did not, itself, influence firing. In freely moving rats, decreased extracellular levels norepinephrine (NE), serotonin (5-HT), and dopamine (DA) frontal cortex hippocampus. selective α2- versus α1-AR antagonists, atipamezole BRL-44408 (a preferential α2A-AR antagonist), elevated NE DA but not 5-HT. presence, on frontocortical NE, DA, 5-HT blocked. contrast, prazosin, a α1- antagonist (which also preferentially blocks α2B/2C-ARs) dose dependently 5-HT, failed to modify actions S18616. Ultrasonic vocalizations elicited rats aversive environment were inhibited S18616, aggressive marble-burying behaviors mice. Furthermore, (biphasically) punished responses Vogel conflict test active social interaction tests rats. At higher doses, displayed sedative/hypnotic properties. Both anxiolytic motor prazosin. Dexmedetomidine mimicked at doses except for more potent Clonidine only markedly doses. conclusion, via activation α2-ARs, potently inhibits corticolimbic adrenergic, serotonergic, (frontocortical) dopaminergic transmission parallel with expression its sedative