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 and Filippo DRAGO. Dopamine D-3 receptor knock-out mice exhibit increased behavioral sensitivity to the anxiolytic drug diazepam. European Neuropsychopharmacology. Amsterdam: Elsevier, 2011, vol. 21, No 4, p. 325-332. ISSN 0924-977X. Available from: https://dx.doi.org/10.1016/j.euroneuro.2010.05.006.

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

• Original language: English
• Type of outcome: Article in a journal
• Field of Study: 30000 3. Medical and Health Sciences
• Country of publisher: Netherlands
• Confidentiality degree: is not subject to a state or trade secret
• Impact factor: Impact factor: 4.046
• Organization unit: Central European Institute of Technology
• Doi: http://dx.doi.org/10.1016/j.euroneuro.2010.05.006
• 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: ne MU
• Tags: International impact, Reviewed

Abstract

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.