5-HT2A and alpha1b-adrenergic receptors entirely mediate dopamine release, locomotor response and behavioural sensitization to opiates and psychostimulants.

Détails

ID Serval
serval:BIB_214C22849800
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
5-HT2A and alpha1b-adrenergic receptors entirely mediate dopamine release, locomotor response and behavioural sensitization to opiates and psychostimulants.
Périodique
European Journal of Neuroscience
Auteur(s)
Auclair A., Drouin C., Cotecchia S., Glowinski J., Tassin J.P.
ISSN
0953-816X (Print)
ISSN-L
0953-816X
Statut éditorial
Publié
Date de publication
2004
Volume
20
Numéro
11
Pages
3073-3084
Langue
anglais
Résumé
Addictive properties of drugs of misuse are generally considered to be mediated by an increased release of dopamine (DA) in the ventral striatum. However, recent experiments indicated an implication of alpha1b-adrenergic receptors in behavioural responses to psychostimulants and opiates. We show now that DA release induced in the ventral striatum by morphine (20 mg/kg) is completely blocked by prazosin (1 mg/kg), an alpha1-adrenergic antagonist. However, morphine-induced increases in DA release in the ventral striatum were found to be similar in mice deleted for the alpha1b-adrenergic receptor (alpha1b-AR KO) and in wild-type (WT) mice, suggesting the presence of a compensatory mechanism. This acute morphine-evoked DA release was completely blocked in alpha1b-AR KO mice by SR46349B (1 mg/kg), a 5-HT2A antagonist. SR46349B also completely blocked, in alpha1b-AR KO mice, the locomotor response and the development of behavioural sensitization to morphine (20 mg/kg) and D-amphetamine (2 mg/kg). Accordingly, the concomitant blockade of 5-HT2A and alpha1b-adrenergic receptors in WT mice entirely blocked acute locomotor responses but also the development of behavioural sensitization to morphine, D-amphetamine or cocaine (10 mg/kg). We observed, nevertheless, that inhibitory effects of each antagonist on locomotor responses to morphine or D-amphetamine were more than additive (160%) in naïve WT mice but not in those sensitized to either drug. Because of these latter data and the possible compensation by 5-HT2A receptors for the genetic deletion of alpha1b-adrenergic receptors, we postulate the existence of a functional link between these receptors, which vanishes during the development of behavioural sensitization.
Mots-clé
Adrenergic alpha-Antagonists/pharmacology, Anesthetics, Local/pharmacology, Animals, Behavior, Animal, Brain Chemistry/drug effects, Central Nervous System Stimulants/pharmacology, Cocaine/pharmacology, Corpus Striatum/drug effects, Dextroamphetamine/pharmacology, Dopamine/metabolism, Drug Administration Schedule, Drug Interactions, Fluorobenzenes/pharmacology, Male, Mice, Mice, Knockout, Microdialysis/methods, Motor Activity/drug effects, Narcotics/pharmacology, Phenols/pharmacology, Prazosin/pharmacology, Receptor, Serotonin, 5-HT2A/metabolism, Receptors, Adrenergic, alpha-1/deficiency, Receptors, Adrenergic, alpha-1/metabolism, Serotonin Antagonists/pharmacology, Time Factors
Pubmed
Web of science
Création de la notice
24/01/2008 11:05
Dernière modification de la notice
20/08/2019 12:57
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