J 2011

Dopamine D-3 receptor knock-out mice exhibit increased behavioral sensitivity to the anxiolytic drug diazepam

LEGGIO, Gian Marc, Vincenzo MICALE, Bernard LE FOLL, Carmen MAZZOLA, Jose N. NOBREGA et. al.

Basic information

Original name

Dopamine D-3 receptor knock-out mice exhibit increased behavioral sensitivity to the anxiolytic drug diazepam

Authors

LEGGIO, Gian Marc, Vincenzo MICALE, Bernard LE FOLL, Carmen MAZZOLA, Jose N. NOBREGA and Filippo DRAGO

Edition

European Neuropsychopharmacology, Amsterdam, Elsevier, 2011, 0924-977X

Other information

Language

English

Type of outcome

Článek v odborném periodiku

Field of Study

30000 3. Medical and Health Sciences

Country of publisher

Netherlands

Confidentiality degree

není předmětem státního či obchodního tajemství

Impact factor

Impact factor: 4.046

Organization unit

Central European Institute of Technology

UT WoS

000289393700006

Keywords in English

Dopamine; D-3 dopamine receptor; Knock-out mice; Diazepam; Elevated plus maze test; Novelty-induced grooming sampling test; GABAA receptor binding

Tags

Tags

International impact, Reviewed
Změněno: 7/8/2012 16:06, Olga Křížová

Abstract

V originále

Dopamine D-3 receptors (DRsD3) seem to have a pivotal role in mood disorders. Using the elevated plus maze (EPM) and the novelty-induced grooming test (NGT), we assessed the responses of DRD3-deficient (D-3(-/-)) mice to the acute treatment (different testing time) with the anxiolytic drug, diazepam. D-3(-/-) mice treated with diazepam (0.1 or 0.5 mg/kg) exhibited a better behavioral response in the EPM than their wild type (WT). Furthermore, in D-3(-/-) mice, but not in WT, 1 mg/kg diazepam induced anxiolytic effects at all testing times. The contribution of DRsD3 in the anxiolytic effects of diazepam was confirmed by similar results obtained in EPM by using the selective DRD3 antagonist U99194A (10 mg/kg) in combination with diazepam, in WT animals. D-3(-/-) mice treated with diazepam (all doses), also showed a decrease in grooming behavior. However, the [H-3] flunitrazepam autoradiographic analysis revealed no significant changes in D-3(-/-) mice compared to WT, suggesting that if gamma-aminobutyric acid receptor GABA(A) changes are involved, they do not occur at the level of binding to benzodiazepine site. These data suggest that D-3(-/-) mice exhibit low baseline anxiety levels and provide the evidence that the DRD3 is involved in the modulation of benzodiazepine anxiolytic effects. (C) 2010 Elsevier B.V. and ECNP. All rights reserved.