Alpha1b-adrenergic receptors control locomotor and rewarding effects of psychostimulants and opiates.

Détails

ID Serval
serval:BIB_B16C08A67C8D
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
Alpha1b-adrenergic receptors control locomotor and rewarding effects of psychostimulants and opiates.
Périodique
Journal of Neuroscience
Auteur(s)
Drouin C., Darracq L., Trovero F., Blanc G., Glowinski J., Cotecchia S., Tassin J.P.
ISSN
1529-2401 (Electronic)
ISSN-L
0270-6474
Statut éditorial
Publié
Date de publication
2002
Volume
22
Numéro
7
Pages
2873-2884
Langue
anglais
Résumé
Drugs of abuse, such as psychostimulants and opiates, are generally considered as exerting their locomotor and rewarding effects through an increased dopaminergic transmission in the nucleus accumbens. Noradrenergic transmission may also be implicated because most psychostimulants increase norepinephrine (NE) release, and numerous studies have indicated interactions between noradrenergic and dopaminergic neurons through alpha1-adrenergic receptors. However, analysis of the effects of psychostimulants after either destruction of noradrenergic neurons or pharmacological blockade of alpha1-adrenergic receptors led to conflicting results. Here we show that the locomotor hyperactivities induced by d-amphetamine (1-3 mg/kg), cocaine (5-20 mg/kg), or morphine (5-10 mg/kg) in mice lacking the alpha1b subtype of adrenergic receptors were dramatically decreased when compared with wild-type littermates. Moreover, behavioral sensitizations induced by d-amphetamine (1-2 mg/kg), cocaine (5-15 mg/kg), or morphine (7.5 mg/kg) were also decreased in knock-out mice when compared with wild-type. Ruling out a neurological deficit in knock-out mice, both strains reacted similarly to novelty, to intraperitoneal saline, or to the administration of scopolamine (1 mg/kg), an anti-muscarinic agent. Finally, rewarding properties could not be observed in knock-out mice in an oral preference test (cocaine and morphine) and conditioned place preference (morphine) paradigm. Because catecholamine tissue levels, autoradiography of D1 and D2 dopaminergic receptors, and of dopamine reuptake sites and locomotor response to a D1 agonist showed that basal dopaminergic transmission was similar in knock-out and wild-type mice, our data indicate a critical role of alpha1b-adrenergic receptors and noradrenergic transmission in the vulnerability to addiction.
Mots-clé
3,4-Dihydroxyphenylacetic Acid/metabolism, Adrenergic alpha-Antagonists/metabolism, Adrenergic alpha-Antagonists/pharmacokinetics, Animals, Brain/drug effects, Brain/metabolism, Central Nervous System Stimulants/pharmacology, Choice Behavior/drug effects, Cocaine/pharmacology, Crosses, Genetic, Dextroamphetamine/pharmacology, Dopamine/metabolism, Dopamine Agonists/pharmacology, Male, Mice, Mice, Inbred Strains, Mice, Knockout, Morphine/pharmacology, Motor Activity/drug effects, Motor Activity/physiology, Muscarinic Antagonists/pharmacology, Narcotics/pharmacology, Norepinephrine/metabolism, Prazosin/pharmacology, Receptors, Adrenergic, alpha-1/deficiency, Receptors, Adrenergic, alpha-1/genetics, Receptors, Dopamine D1/agonists, Receptors, Dopamine D1/metabolism, Receptors, Dopamine D2/metabolism, Reward, Substance-Related Disorders/etiology, Substance-Related Disorders/metabolism, Synaptic Transmission/physiology
Pubmed
Web of science
Création de la notice
24/01/2008 11:05
Dernière modification de la notice
20/08/2019 15:20
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