Behavioural and Anatomical Characterization of Mutant Mice With Targeted Deletion of D1 Dopamine Receptor–Expressing Cells: Response to Acute Morphine
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 expressin...
| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2013-01-01
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| Series: | Journal of Pharmacological Sciences |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S1347861319304025 |
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| author | Daniela Babovic Luning Jiang Satoshi Goto Ilse Gantois Günter Schütz Andrew J. Lawrence John L. Waddington John Drago |
| author_facet | Daniela Babovic Luning Jiang Satoshi Goto Ilse Gantois Günter Schütz Andrew J. Lawrence John L. Waddington John Drago |
| author_sort | Daniela Babovic |
| collection | DOAJ |
| description | 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. Keywords:: basal ganglia, morphine, dopamine, striatum |
| first_indexed | 2024-12-19T19:23:46Z |
| format | Article |
| id | doaj.art-27b01a8dd3ee465f81565a807fca6f0e |
| institution | Directory Open Access Journal |
| issn | 1347-8613 |
| language | English |
| last_indexed | 2024-12-19T19:23:46Z |
| publishDate | 2013-01-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Journal of Pharmacological Sciences |
| spelling | doaj.art-27b01a8dd3ee465f81565a807fca6f0e2022-12-21T20:08:52ZengElsevierJournal of Pharmacological Sciences1347-86132013-01-0112113947Behavioural and Anatomical Characterization of Mutant Mice With Targeted Deletion of D1 Dopamine Receptor–Expressing Cells: Response to Acute MorphineDaniela Babovic0Luning Jiang1Satoshi Goto2Ilse Gantois3Günter Schütz4Andrew J. Lawrence5John L. Waddington6John Drago7Molecular & Cellular Therapeutics, Royal College of Surgeons in Ireland, Dublin 2, IrelandFlorey Neuroscience Institute, The University of Melbourne, Victoria 3010, Australia; Centre for Neuroscience, The University of Melbourne, Victoria 3010, AustraliaParkinson’s Disease and Dystonia Research Center, Institute of Health Biosciences, Graduate School of Medical Sciences, University of Tokushima, Tokushima 770-8503, JapanFlorey Neuroscience Institute, The University of Melbourne, Victoria 3010, AustraliaDeutsches Krebsforschungszentrum, 69120 Heidelberg, GermanyFlorey Neuroscience Institute, The University of Melbourne, Victoria 3010, Australia; Centre for Neuroscience, The University of Melbourne, Victoria 3010, AustraliaMolecular & Cellular Therapeutics, Royal College of Surgeons in Ireland, Dublin 2, IrelandFlorey Neuroscience Institute, The University of Melbourne, Victoria 3010, Australia; Centre for Neuroscience, The University of Melbourne, Victoria 3010, Australia; Corresponding author. john.drago@florey.edu.auConsiderable 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. Keywords:: basal ganglia, morphine, dopamine, striatumhttp://www.sciencedirect.com/science/article/pii/S1347861319304025 |
| spellingShingle | Daniela Babovic Luning Jiang Satoshi Goto Ilse Gantois Günter Schütz Andrew J. Lawrence John L. Waddington John Drago Behavioural and Anatomical Characterization of Mutant Mice With Targeted Deletion of D1 Dopamine Receptor–Expressing Cells: Response to Acute Morphine Journal of Pharmacological Sciences |
| title | Behavioural and Anatomical Characterization of Mutant Mice With Targeted Deletion of D1 Dopamine Receptor–Expressing Cells: Response to Acute Morphine |
| title_full | Behavioural and Anatomical Characterization of Mutant Mice With Targeted Deletion of D1 Dopamine Receptor–Expressing Cells: Response to Acute Morphine |
| title_fullStr | Behavioural and Anatomical Characterization of Mutant Mice With Targeted Deletion of D1 Dopamine Receptor–Expressing Cells: Response to Acute Morphine |
| title_full_unstemmed | Behavioural and Anatomical Characterization of Mutant Mice With Targeted Deletion of D1 Dopamine Receptor–Expressing Cells: Response to Acute Morphine |
| title_short | Behavioural and Anatomical Characterization of Mutant Mice With Targeted Deletion of D1 Dopamine Receptor–Expressing Cells: Response to Acute Morphine |
| title_sort | behavioural and anatomical characterization of mutant mice with targeted deletion of d1 dopamine receptor expressing cells response to acute morphine |
| url | http://www.sciencedirect.com/science/article/pii/S1347861319304025 |
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