期刊论文详细信息
Journal of Pharmacological Sciences
Behavioural and Anatomical Characterization of Mutant Mice With Targeted Deletion of D1 Dopamine Receptor–Expressing Cells: Response to Acute Morphine
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
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【 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.

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