Stimulation of the β3-Adrenoceptor as a Novel Treatment Strategy for Anxiety and Depressive Disorders

Autor: R. Alonso, Guy Griebel, Bernard Scatton, Patrick Avenet, Dominique Françon, Gérard Le Fur, Olivier Bergis, Jeanne Stemmelin, Vincent Santucci, Matilde Lopez-Grancha, Caroline Cohen, Michel Decobert, Philippe Pichat, Terranova Jean-Paul, P.E. Keane, Stephen M. Stahl
Rok vydání: 2007
Předmět:
Male
Imipramine
Morris water navigation task
Poison control
Antidepressive Agents
Tricyclic
Pharmacology
Rats
Sprague-Dawley
Mice
Cognition
Mice
Knockout
Mice
Inbred BALB C
Behavior
Animal
Adrenergic beta-Agonists
Anxiety Disorders
Aggression
Psychiatry and Mental health
Anesthesia
Antidepressive Agents
Second-Generation
Antidepressant
Psychology
Anxiety disorder
medicine.drug
Tetrahydronaphthalenes
Substance-Related Disorders
medicine.drug_class
Adrenergic beta-3 Receptor Agonists
Motor Activity
Anxiolytic
Chlordiazepoxide
Amibegron
Fluoxetine
medicine
Animals
Interpersonal Relations
Rats
Long-Evans
Rats
Wistar
Swimming
Depressive Disorder
Benzodiazepine
Diazepam
Ethanol
medicine.disease
Rats
Mice
Inbred C57BL
Anti-Anxiety Agents
Receptors
Adrenergic
beta-3
Exploratory Behavior
Gerbillinae
Sleep
Zdroj: Neuropsychopharmacology. 33:574-587
ISSN: 1740-634X
0893-133X
Popis: The characterization of the first selective orally active and brain-penetrant beta3-adrenoceptor agonist, SR58611A (amibegron), has opened new possibilities for exploring the involvement of this receptor in stress-related disorders. By using a battery of tests measuring a wide range of anxiety-related behaviors in rodents, including the mouse defense test battery, the elevated plus-maze, social interaction, stress-induced hyperthermia, four-plate, and punished drinking tests, we demonstrated for the first time that the stimulation of the beta3 receptor by SR58611A resulted in robust anxiolytic-like effects, with minimal active doses ranging from 0.3 to 10 mg/kg p.o., depending on the procedure. These effects paralleled those obtained with the prototypical benzodiazepine anxiolytic diazepam or chlordiazepoxide. Moreover, when SR58611A was tested in acute or chronic models of depression in rodents, such as the forced-swimming and the chronic mild stress tests, it produced antidepressant-like effects, which were comparable in terms of the magnitude of the effects to those of the antidepressant fluoxetine or imipramine. Supporting these behavioral data, SR58611A modified spontaneous sleep parameters in a manner comparable to that observed with fluoxetine. Importantly, SR58611A was devoid of side effects related to cognition (as shown in the Morris water maze and object recognition tasks), motor activity (in the rotarod), alcohol interaction, or physical dependence. Antagonism studies using pharmacological tools targeting a variety of neurotransmitters involved in anxiety and depression and the use of mice lacking the beta3 adrenoceptor suggested that these effects of SR58611A are mediated by beta3 adrenoceptors. Taken as a whole, these findings indicate that the pharmacological stimulation of beta3 adrenoceptors may represent an innovative approach for the treatment of anxiety and depressive disorders.
Databáze: OpenAIRE
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