D-amphetamine fails to increase extracellular dopamine levels in mice lacking alpha 1b-adrenergic receptors: relationship between functional and nonfunctional dopamine release.

Détails

ID Serval
serval:BIB_032550D14A13
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
D-amphetamine fails to increase extracellular dopamine levels in mice lacking alpha 1b-adrenergic receptors: relationship between functional and nonfunctional dopamine release.
Périodique
Journal of Neuroscience
Auteur(s)
Auclair A., Cotecchia S., Glowinski J., Tassin J.P.
ISSN
1529-2401 (Electronic)
ISSN-L
0270-6474
Statut éditorial
Publié
Date de publication
2002
Volume
22
Numéro
21
Pages
9150-9154
Langue
anglais
Résumé
It was found recently that locomotor and rewarding effects of psychostimulants and opiates were dramatically decreased or suppressed in mice lacking alpha1b-adrenergic receptors [alpha1b-adrenergic receptor knock-outs (alpha1bAR-KOs)] (Drouin et al., 2002). Here we show that blunted locomotor responses induced by 3 and 6 mg/kg d-amphetamine in alpha1bAR-KO mice [-84 and -74%, respectively, when compared with wild-type (WT) mice] are correlated with an absence of d-amphetamine-induced increase in extracellular dopamine (DA) levels in the nucleus accumbens of alpha1bAR-KO mice. Moreover, basal extracellular DA levels in the nucleus accumbens are lower in alpha1bAR-KO than in WT littermates (-28%; p < 0.001). In rats however, prazosin, an alpha1-adrenergic antagonist, decreases d-amphetamine-induced locomotor hyperactivity without affecting extracellular DA levels in the nucleus accumbens, a finding related to the presence of an important nonfunctional release of DA (Darracq et al., 1998). We show here that local d-amphetamine releases nonfunctional DA with the same affinity but a more than threefold lower amplitude in C57BL6/J mice than in Sprague Dawley rats. Altogether, this suggests that a trans-synaptic mechanism amplifies functional DA into nonfunctional DA release. Our data confirm the presence of a powerful coupling between noradrenergic and dopaminergic neurons through the stimulation of alpha1b-adrenergic receptors and indicate that nonfunctional DA release is critical in the interpretation of changes in extracellular DA levels. These results suggest that alpha1b-adrenergic receptors may be important therapeutic pharmacological targets not only in addiction but also in psychosis because most neuroleptics possess anti-alpha1-adrenergic properties.
Mots-clé
Animals, Behavior, Animal/drug effects, Dextroamphetamine/pharmacology, Dopamine/analysis, Dopamine/metabolism, Dose-Response Relationship, Drug, Extracellular Space/chemistry, Extracellular Space/metabolism, Male, Mice, Mice, Inbred C57BL, Mice, Knockout, Microdialysis, Motor Activity/drug effects, Nucleus Accumbens/cytology, Nucleus Accumbens/drug effects, Perfusion, Rats, Rats, Sprague-Dawley, Receptors, Adrenergic, alpha-1/deficiency, Receptors, Adrenergic, alpha-1/genetics, Species Specificity
Pubmed
Web of science
Création de la notice
24/01/2008 11:05
Dernière modification de la notice
20/08/2019 12:25
Données d'usage