Apparent dopamine D1 and D2 receptors in the weaver mutant mouse: receptor binding and coupling to adenylyl cyclase.
Weaver mutant mice have a selective degeneration of the nigrostriatal dopamine pathway arising between 7-21 days after birth. The goal of this study was to investigate the effects of this mutation on different parameters of the nigrostriatal and mesolimbic dopamine system: apparent D1 and D2 receptor binding sites as well as their signal transduction pathway. Using quantitative autoradiography of ligands for dopamine D1, D2 receptors and the dopamine uptake site, we found a significant loss in apparent D1 receptor binding sites throughout the neostriatum, significant increase of apparent D2 receptor binding in the dorsal aspect of the neostriatum, and almost complete loss of DA uptake sites in these regions of the weaver mouse. In contrast to the neostriatum, the density of dopamine receptors and uptake sites in the nucleus accumbens of the weaver mouse did not differ from controls. Despite alterations in the binding of apparent D1 and D2 receptors, there was no significant difference in either basal, DA stimulated or GTPgammaS stimulated cAMP production. These findings suggest the down-regulation of apparent D1 receptor binding sites reported in this model, probably does not reflect an important physiological mechanism through which these animals compensate for loss of dopamine innervation.
Dewar
K M
KM
Hôpital Louis-H. Lafontaine, Département de Psychiatrie, Université de Montréal, Québec, Canada.
Paquet
M
M
Sequeira
A
A
D000262:Adenylyl Cyclases / Q000378:metabolism*; D000818:Animals; D001345:Autoradiography; D001549:Benzamides / Q000493:pharmacokinetics; D001552:Benzazepines / Q000493:pharmacokinetics; D003042:Cocaine / Q000031:analogs & derivatives / Q000493:pharmacokinetics; D003342:Corpus Striatum / Q000378:metabolism* / Q000503:physiopathology; D000242:Cyclic AMP / Q000378:metabolism; D004298:Dopamine / Q000378:metabolism* / Q000494:pharmacology; D018492:Dopamine Antagonists / Q000493:pharmacokinetics; D015536:Down-Regulation; D016244:Guanosine 5'-O-(3-Thiotriphosphate) / Q000494:pharmacology; D008032:Limbic System / Q000378:metabolism* / Q000503:physiopathology; D051379:Mice; D008818:Mice, Neurologic Mutants; D009410:Nerve Degeneration / Q000235:genetics / Q000503:physiopathology; D009714:Nucleus Accumbens / Q000378:metabolism / Q000503:physiopathology; D017447:Receptors, Dopamine D1 / Q000378:metabolism / Q000502:physiology*; D017448:Receptors, Dopamine D2 / Q000378:metabolism / Q000502:physiology*; D012016:Reference Values; D015398:Signal Transduction; D013378:Substantia Nigra / Q000378:metabolism* / Q000503:physiopathology; D014316:Tritium
D001549:Benzamides; D001552:Benzazepines; D018492:Dopamine Antagonists; D017447:Receptors, Dopamine D1; D017448:Receptors, Dopamine D2; D014316:Tritium; D016244:Guanosine 5'-O-(3-Thiotriphosphate); C021279:(1R-(exo,exo))-3-(4-fluorophenyl)-8-methyl-8- azabicyclo(3.2.1)octane-2-carboxylic acid, methyl ester; D000242:Cyclic AMP; D000262:Adenylyl Cyclases; D003042:Cocaine; C030265:nemonapride; D004298:Dopamine