Behavioural and Anatomical Characterization of Mutant Mice With Targeted Deletion of D1 Dopamine Receptor–Expressing Cells: Response to Acute Morphine

Journal of Pharmacological Sciences

Günter Schütz²  Ilse Gantois³  John L. Waddington⁴  Andrew J. Lawrence³  Babovic Daniela⁴  John Drago³  Satoshi Goto¹  Luning Jiang³ 

[1] Parkinson’s Disease and Dystonia Research Center, Institute of Health Biosciences, Graduate School of Medical Sciences, University of Tokushima, Japan;Deutsches Krebsforschungszentrum, Germany;Florey Neuroscience Institute, The University of Melbourne, Australia;Molecular & Cellular Therapeutics, Royal College of Surgeons in Ireland, Ireland

关键词: basal ganglia;    morphine;    dopamine;    striatum;   

DOI  :  10.1254/jphs.12214FP

学科分类：药学

来源: Nihon Yakuri Gakkai Henshuubu / Japanese Pharmacological Society

【 摘 要 】

References(47)Cited-By(3)Considerable topographic overlap exists between brain opioidergic and dopaminergic neurons. Pharmacological blockade of the dopamine D1 receptor (Drd1a) reverses several behavioural phenomena elicited by opioids. The present study examines the effects of morphine in adult mutant (MUT) mice expressing the attenuated diphtheria toxin-176 gene in Drd1a-expressing cells, a mutant line shown previously to undergo post-natal striatal atrophy and loss of Drd1a-expression. MUT and wild-type mice were assessed behaviourally following acute administration of 10 mg/kg morphine. Treatment with morphine reduced locomotion and rearing similarly in both genotypes but reduced total grooming only in MUT mice. Morphine-induced Straub tail and stillness were heightened in MUT mice. Chewing and sifting were decreased in MUT mice and these effects were not modified by morphine. Loss of striatal Drd1-positive cells and up-regulated D2-expression, as reflected in down-regulated D1-like and up-regulated D2-like binding, respectively, is not uniform along the cranio-caudal extent in this model but appears to be greater in the caudal striatum. Preferential caudal loss of μ-opioid-expression, a marker for the striosomal compartment, was seen. These data indicate that Drd1a-positive cell loss modifies the exploratory behavioural response elicited by morphine, unmasking novel morphine-induced MUT-specific behaviours and generating a hypersensitivity to morphine for others.

【 授权许可】

Unknown