title: Simultaneous activation of the α1A-, α1B- and α1D-adrenoceptor subtypes in the nucleus accumbens reduces accumbal dopamine efflux in freely moving rats.
abstract: Intra-accumbal infusion of the α1-adrenergic agonist methoxamine, which has comparable affinity for α1A-, α1B- and α1D-adrenoceptor subtypes, fails to alter noradrenaline efflux but reduces dopamine efflux in the nucleus accumbens of rats. In-vivo microdialysis experiments were carried out to analyse the putative contribution of α1A-, α1B- and α1D-adrenoceptor subtypes to the methoxamine-induced decrease in accumbal dopamine efflux in freely moving rats. The drugs used were dissolved in the infusion medium and administered locally through a dialysis membrane. Intra-accumbal infusions of the α1A-adrenoceptor antagonist 5-methylurapidil (6 pmol), the α1B-adrenoceptor antagonist cyclazosin (0.6 and 6 pmol) and the α1D-adrenoceptor antagonist BMY 7378 (0.6 pmol) did not alter accumbal efflux of noradrenaline or dopamine: pretreatment with each of these α1-adrenoceptor subtype-selective antagonists counteracted the methoxamine (24 pmol)-induced decrease in accumbal dopamine efflux. Doses indicated are the total amount of drug administered over a 60-min infusion period. These results clearly suggest that the α1A-, α1B- and α1D-adrenoceptor subtypes in the nucleus accumbens mediate the α1-adrenergic agonist methoxamine-induced decrease in accumbal dopamine efflux. The present study also provides in-vivo neurochemical evidence indicating that concomitant, but not separate, activation of the α1A-, α1B- and α1D-adrenoceptors in the nucleus accumbens is required for α1-adrenergic inhibition of accumbal dopaminergic activity.
authors.affiliation: aDepartment of Pharmacology, Nihon University School of Dentistry at Matsudo, Chiba Departments of bPharmacology cOrthodontics dAnaesthesiology ePediatric Dentistry fDivision of Oral and Craniomaxillofacial Research, Dental Research Centre, Nihon University School of Dentistry, Tokyo, Japan gDepartment of Cognitive Neuroscience, Radboud University Medical Centre Nijmegen, Division of Psychoneuropharmacology, Donders Institute for Brain, Cognition, and Behaviour, Nijmegen, The Netherlands.
authors.forename: Yuri
authors.initials: Y
authors.lastname: Aono
authors.forename: Hiroko
authors.initials: H
authors.lastname: Taguchi
authors.forename: Tadashi
authors.initials: T
authors.lastname: Saigusa
authors.forename: Takuya
authors.initials: T
authors.lastname: Uchida
authors.forename: Koji
authors.initials: K
authors.lastname: Takada
authors.forename: Hatakazu
authors.initials: H
authors.lastname: Takiguchi
authors.forename: Tetsuo
authors.initials: T
authors.lastname: Shirakawa
authors.forename: Noriyoshi
authors.initials: N
authors.lastname: Shimizu
authors.forename: Noriaki
authors.initials: N
authors.lastname: Koshikawa
authors.forename: Alexander R
authors.initials: AR
authors.lastname: Cools
mesh_terms: D000317:Adrenergic alpha-Antagonists / Q000008:administration & dosage / Q000494:pharmacology; D058665:Adrenergic beta-1 Receptor Agonists / Q000494:pharmacology*; D000818:Animals; D004298:Dopamine / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D008297:Male; D008729:Methoxamine / Q000494:pharmacology*; D017551:Microdialysis; D009714:Nucleus Accumbens / Q000187:drug effects* / Q000378:metabolism; D010879:Piperazines / Q000494:pharmacology; D011799:Quinazolines / Q000008:administration & dosage / Q000494:pharmacology; D011810:Quinoxalines / Q000008:administration & dosage / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D018340:Receptors, Adrenergic, alpha-1 / Q000187:drug effects* / Q000378:metabolism
chemical_list: D000317:Adrenergic alpha-Antagonists; D058665:Adrenergic beta-1 Receptor Agonists; D010879:Piperazines; D011799:Quinazolines; D011810:Quinoxalines; D018340:Receptors, Adrenergic, alpha-1; C080462:cyclazosin; C057446:5-methylurapidil; D008729:Methoxamine; C053428:BMY 7378; D004298:Dopamine