title: Critical role of alpha1-adrenergic receptors in acute and sensitized locomotor effects of D-amphetamine, cocaine, and GBR 12783: influence of preexposure conditions and pharmacological characteristics.
abstract: Psychostimulant-induced locomotor hyperactivity is commonly associated with an inhibition of dopamine reuptake. However, a physiological coupling between noradrenergic and dopaminergic neurons occurring through the stimulation of alpha1-adrenergic receptors has recently been proposed. This possibility was tested on locomotor responses induced either by D-amphetamine and cocaine, which both interfere with noradrenergic and dopaminergic transmissions, or by GBR 12783, a specific dopamine reuptake inhibitor. In an attempt to control the effects of stress and novelty on noradrenergic neurons activity, rats were submitted to habituation procedures consisting of either a 15-h period of habituation to the experimental environment ("long-habituation") or to repeated exposure to intraperitoneal saline injections for 3 consecutive days ("three-session"). Three-session-exposed animals exhibited a pronounced locomotor reactivity to saline injection which did not occur after noradrenergic depletion, clonidine (20 microg/kg) or prazosin (0.5 mg/kg) pretreatments, or in long-habituation-preexposed animals. Cocaine and GBR 12783 locomotor hyperactivities were doubled in three-session vs. long-habituation-preexposed rats, whereas D-amphetamine responses were similar in both conditions. Prazosin (0.5 mg/kg) pretreatment reduced the acute locomotor effects of the three psychostimulants in both procedures and blocked the behavioral sensitization induced by repeated injections of D-amphetamine (0.75 mg/kg) or cocaine (5 mg/kg). GBR 12783 (5 mg/kg) failed to induce significant behavioral sensitization. In addition to their role in the acute and sensitized locomotor responses to psychostimulants possessing different pharmacological characteristics, alpha1-adrenergic receptors are involved in animal reactivity to previously experimented procedures. This suggests an implication of noradrenergic neurons in the vulnerability to psychostimulants.
authors.affiliation: Chaire de Neuropharmacologie, INSERM U114, Collège de France, 75005 Paris, France.
authors.forename: Candice
authors.initials: C
authors.lastname: Drouin
authors.forename: Gérard
authors.initials: G
authors.lastname: Blanc
authors.forename: Anne-Sophie
authors.initials: AS
authors.lastname: Villégier
authors.forename: Jacques
authors.initials: J
authors.lastname: Glowinski
authors.forename: Jean-Pol
authors.initials: JP
authors.lastname: Tassin
mesh_terms: D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000661:Amphetamine / Q000494:pharmacology; D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D003042:Cocaine / Q000494:pharmacology; D004298:Dopamine / Q000378:metabolism*; D018765:Dopamine Uptake Inhibitors / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D004347:Drug Interactions / Q000502:physiology; D004361:Drug Tolerance / Q000502:physiology*; D006185:Habituation, Psychophysiologic / Q000502:physiology; D006948:Hyperkinesis / Q000139:chemically induced* / Q000378:metabolism / Q000503:physiopathology; D008297:Male; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D009638:Norepinephrine / Q000378:metabolism*; D010879:Piperazines / Q000494:pharmacology; D011224:Prazosin / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D018340:Receptors, Adrenergic, alpha-1 / Q000187:drug effects* / Q000378:metabolism; D012965:Sodium Chloride / Q000494:pharmacology; D009435:Synaptic Transmission / Q000187:drug effects* / Q000502:physiology
chemical_list: D000317:Adrenergic alpha-Antagonists; D018765:Dopamine Uptake Inhibitors; D010879:Piperazines; D018340:Receptors, Adrenergic, alpha-1; D012965:Sodium Chloride; C039737:1-(2-(diphenylmethoxy)ethyl)-4-(3-phenyl-2-propenyl)piperazine; D000661:Amphetamine; D003042:Cocaine; D004298:Dopamine; D009638:Norepinephrine; D011224:Prazosin