Publication details

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

Authors

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

Year of publication 2011
Type Article in Periodical
Magazine / Source European Neuropsychopharmacology
MU Faculty or unit

Central European Institute of Technology

Citation
Doi http://dx.doi.org/10.1016/j.euroneuro.2010.05.006
Field Neurology, neurosurgery, neurosciences
Keywords Dopamine; D-3 dopamine receptor; Knock-out mice; Diazepam; Elevated plus maze test; Novelty-induced grooming sampling test; GABAA receptor binding
Description 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.

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