title: Role of epinephrine stimulation of CNS alpha1-adrenoceptors in motor activity in mice.
abstract: The role of brain epinephrine (EPI) in the regulation of motor activity and movement in mice was examined. Blockade of EPI synthesis with i.p. 2,3-dichloro-alpha-methylbenzylamine (DCMB) or LY134046 was found to produce marked behavioral inactivity which could be significantly reversed by intraventricular injection of EPI and by three other alpha(1)-adrenoceptor agonists, norepinephrine (NE), 6-fluoronorepinephrine (6FNE), and phenylephrine (PE), as well as by serotonin (5HT). EPI had the largest effect of these agonists and also was the only one that reversed nondrug-induced inactivity of mice in their home cages during the light phase. The effects of EPI were blocked by coinfusion of an alpha(1)-adrenoceptor antagonist (terazosin) but not of an alpha(2)-(atipamezole) or beta(1) (betaxolol)-blocker. The rank order of maximal behavioral responses to EPI, 6FNE, and PE in DCMB-treated mice was the same as the rank order of their maximal stimulation of hydrolysis of phosphatidylinositol at cloned alpha(1B)-adrenoceptors in cell culture. On the basis of the above findings and of the central distributions of adrenergic neurons and alpha(1)-adrenoceptors, the existence of a central EPI-innervated alpha(1)-adrenergic receptor system is postulated which serves to coexcite or enhance signaling in several monoaminergic brain regions involved in movement and motor activity.
authors.affiliation: Department of Psychiatry, New York University School of Medicine, New York, New York 10016, USA. es35@nyu.edu
authors.forename: Eric A
authors.initials: EA
authors.lastname: Stone
authors.forename: Gary L
authors.initials: GL
authors.lastname: Grunewald
authors.forename: Yan
authors.initials: Y
authors.lastname: Lin
authors.forename: Rashedul
authors.initials: R
authors.lastname: Ahsan
authors.forename: Helen
authors.initials: H
authors.lastname: Rosengarten
authors.forename: H Kenneth
authors.initials: HK
authors.lastname: Kramer
authors.forename: David
authors.initials: D
authors.lastname: Quartermain
mesh_terms: D000316:Adrenergic alpha-Agonists / Q000494:pharmacology*; D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology*; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000818:Animals; D001596:Benzylamines / Q000494:pharmacology; D015784:Betaxolol / Q000494:pharmacology; D001921:Brain / Q000187:drug effects*; D002460:Cell Line; D004837:Epinephrine / Q000008:administration & dosage / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D006801:Humans; D006868:Hydrolysis; D007093:Imidazoles / Q000494:pharmacology; D007276:Injections, Intraventricular; D007668:Kidney / Q000187:drug effects / Q000378:metabolism; D008297:Male; D051379:Mice; D009043:Motor Activity / Q000187:drug effects*; D009638:Norepinephrine / Q000031:analogs & derivatives* / Q000494:pharmacology; D010656:Phenylephrine / Q000494:pharmacology; D010716:Phosphatidylinositols / Q000378:metabolism; D011224:Prazosin / Q000031:analogs & derivatives* / Q000494:pharmacology; D011942:Receptors, Adrenergic, alpha / Q000187:drug effects / Q000378:metabolism*; D012701:Serotonin / Q000494:pharmacology
chemical_list: D000316:Adrenergic alpha-Agonists; D000317:Adrenergic alpha-Antagonists; D000319:Adrenergic beta-Antagonists; D001596:Benzylamines; D007093:Imidazoles; D010716:Phosphatidylinositols; D011942:Receptors, Adrenergic, alpha; C050701:atipamezole; D010656:Phenylephrine; D012701:Serotonin; C002569:2,3-dichloro-alpha-methylbenzylamine; C024884:6-fluoronorepinephrine; C041226:Terazosin; D015784:Betaxolol; D009638:Norepinephrine; D011224:Prazosin; D004837:Epinephrine