Adaptive changes in postsynaptic dopamine receptors despite unaltered dopamine dynamics in mice lacking monoamine oxidase B.
Monoamine oxidase (MAO) B is considered a key enzyme in dopamine metabolism. The present studies, conducted in MAO B knockout mice, show that lack of MAO B does not alter extracellular levels of dopamine in striatum. Similarly, the synthesis, storage, uptake, and release of dopamine are also unaltered. However, autoradiography revealed a significant up-regulation of the D2-like dopamine receptors in the striatum of MAO B knockout mice. Mutant mice also exhibit a functional supersensitivity of D1-dopamine receptors in the nucleus accumbens. Thus, the agonist SKF 38,393-induced c-Fos immunoreactivity was significantly increased in knockout mice as compared with wild-type controls. In view of the apparently normal basal dopamine dynamics observed in MAO B knockout mice, we hypothesize that a dopamine-independent mechanism underlies adaptations in dopamine receptor function that occur as a consequence of MAO B depletion. Finally, these findings suggest that chronic administration of MAO inhibitors, as occurs in the treatment of Parkinson's disease and depression, may be associated with an increased responsiveness of CNS neurons to dopamine receptor ligands.
Chen
L
L
Department of Pharmacology, Weill Medical College of Cornell University, New York, NY 10021, USA.
He
M
M
Sibille
E
E
Thompson
A
A
Sarnyai
Z
Z
Baker
H
H
Shippenberg
T
T
Toth
M
M
D000818:Animals; D000906:Antibodies; D001345:Autoradiography; D002352:Carrier Proteins / Q000032:analysis / Q000378:metabolism; D004298:Dopamine / Q000378:metabolism*; D050483:Dopamine Plasma Membrane Transport Proteins; D015971:Gene Expression Regulation, Enzymologic; D007457:Iodine Radioisotopes; D008297:Male; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D051379:Mice; D018345:Mice, Knockout; D017551:Microdialysis; D008995:Monoamine Oxidase / Q000235:genetics*; D009419:Nerve Tissue Proteins; D009714:Nucleus Accumbens / Q000737:chemistry / Q000201:enzymology; D016760:Proto-Oncogene Proteins c-fos / Q000032:analysis; D011869:Radioligand Assay; D017447:Receptors, Dopamine D1 / Q000378:metabolism*; D017448:Receptors, Dopamine D2 / Q000378:metabolism*; D013570:Synaptic Membranes / Q000737:chemistry / Q000201:enzymology*; D014446:Tyrosine 3-Monooxygenase / Q000032:analysis / Q000276:immunology; D015854:Up-Regulation / Q000502:physiology
D000906:Antibodies; D002352:Carrier Proteins; D050483:Dopamine Plasma Membrane Transport Proteins; D007457:Iodine Radioisotopes; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins; D016760:Proto-Oncogene Proteins c-fos; D017447:Receptors, Dopamine D1; D017448:Receptors, Dopamine D2; D014446:Tyrosine 3-Monooxygenase; D008995:Monoamine Oxidase; D004298:Dopamine