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

Details

Serval ID
serval:BIB_214C22849800
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
5-HT2A and alpha1b-adrenergic receptors entirely mediate dopamine release, locomotor response and behavioural sensitization to opiates and psychostimulants.
Journal
European Journal of Neuroscience
Author(s)
Auclair A., Drouin C., Cotecchia S., Glowinski J., Tassin J.P.
ISSN
0953-816X (Print)
ISSN-L
0953-816X
Publication state
Published
Issued date
2004
Volume
20
Number
11
Pages
3073-3084
Language
english
Abstract
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.
Keywords
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
Create date
24/01/2008 11:05
Last modification date
20/08/2019 12:57
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