title: Evidence that behavioural and electrocortical sleep induced by guanfacine is due to stimulation of alpha 2-adrenoceptors.
abstract: The effects of guanfacine and other drugs acting at alpha 1- and alpha 2-adrenoceptors on behaviour, electrocortical activity and ECoG spectrum power were studied in chicks and rats. Guanfacine, given systematically in chicks, produced behavioural and electrocortical slow-wave sleep lasting 100-200 min, depending on the dose; these effects were prevented by yohimbine, a selective antagonist, at alpha 2-adrenoceptors and potentiated by prazosin, a selective antagonist, at alpha 1-adrenoceptors. Similar behavioural and electrocortical effects were obtained after systemic or intraventricular infusion of guanfacine in rats. In addition, a significant increase in total and in lower frequency band (0-4; 4-8 Hz) voltage power was observed. Behavioural and ECoG effects of guanfacine were prevented by phentolamine or yohimbine, whereas prazosin and propranolol were ineffective. Yohimbine itself, given systemically in chicks, produced behavioural stimulation, vocalization, increase in locomotor activity and ECoG desynchronization, with a significant fall in total and 0-3, 3-6, 6-9 and 9-12 Hz voltage power lasting approx. 3 h. Desipramine, an inhibitor of noradrenaline reuptake, produced in chicks behavioural and ECoG arousal, vocalization, pecking, escape responses and aggressive behaviour. In conclusion, the present experiments show that guanfacine sedative effects seem to be mediated predominantly via an activation of presynaptic alpha 2-adrenoceptors and suggest that arousal is due to stimulation of post-synaptic alpha 1-adrenoceptors.
mesh_terms: D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D002540:Cerebral Cortex / Q000187:drug effects*; D002645:Chickens; D004305:Dose-Response Relationship, Drug; D005071:Evoked Potentials / Q000187:drug effects; D016316:Guanfacine; D006146:Guanidines / Q000494:pharmacology*; D007276:Injections, Intraventricular; D010646:Phentolamine / Q000494:pharmacology; D010648:Phenylacetates / Q000494:pharmacology*; D011224:Prazosin / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D011942:Receptors, Adrenergic, alpha / Q000187:drug effects*; D012894:Sleep Stages / Q000187:drug effects*; D015016:Yohimbine / Q000494:pharmacology
chemical_list: D006146:Guanidines; D010648:Phenylacetates; D011942:Receptors, Adrenergic, alpha; D015016:Yohimbine; D016316:Guanfacine; D011224:Prazosin; D010646:Phentolamine