Dopamine D3 receptor knock-out mice exhibit increased behavioral sensitivity to the anxiolytic drug diazepam

European Neuropsychopharmacology : the Journal of the European College of Neuropsychopharmacology
Gian Marco LeggioFilippo Drago

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 0.5mg/kg) exhibited a better behavioral response in the EPM than their wild type (WT). Furthermore, in D(3)(-/-) mice, but not in WT, 1mg/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 (10mg/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 [(3)H]flunitrazepam autoradiographic analysis revealed no significant changes in D(3)(-/-) mice compared to WT, suggesting that if γ-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 inv...Continue Reading

Citations

Sep 1, 1997·Pharmacology, Biochemistry, and Behavior·L L Miner
Apr 25, 2012·Neurobiology of Disease·Thibault RenoirAnthony J Hannan
Jun 10, 2014·Physiology & Behavior·A Ennaceur
Jan 30, 2013·Behavioural Brain Research·Bo XingYong-hui Dang
Dec 9, 2014·European Neuropsychopharmacology : the Journal of the European College of Neuropsychopharmacology·Gian Marco LeggioSalvatore Salomone
Aug 12, 2014·Behavioural Brain Research·Rodrigo Moraga-AmaroJimmy Stehberg
Jul 23, 2013·European Journal of Pharmacology·Gian Marco LeggioFilippo Drago
Jun 23, 2016·Neuroscience and Biobehavioral Reviews·Farhan MohammadAdam Claridge-Chang
Jun 28, 2016·Pharmacology & Therapeutics·Gian Marco LeggioFilippo Drago
Oct 20, 2017·Frontiers in Pharmacology·Sebastiano Alfio TorrisiGian Marco Leggio
May 28, 2021·Expert Opinion on Pharmacotherapy·Gustavo A AngaritaMarc N Potenza

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