In vitro release of endogenous dopamine from the striatum of the weaver mutant mouse.
The weaver mutant mouse has a genetically determined defect in the nigrostriatal dopaminergic system. The present study was undertaken to test the hypothesis that in the weaver mutant mouse, striatal nerve terminals undergo compensatory changes in response to this deficiency. To test this hypothesis, we studied the basal and stimulated release of dopamine from striatal slices of weaver mutant mice and matched controls. By using a superfusion system and concentrating the superfusate by passage over alumina, resting dopamine release could be determined in the weaver mutant despite the fact that striatal tissue content of dopamine in these mice is reduced by greater than 75% compared with control mice. Fractional resting release of dopamine in weaver striatal slices was significantly elevated compared with that in controls, suggesting that the release mechanisms in the weaver may be adapting to overcome the dopamine deficit. Potassium-evoked release (24 and 48 mM potassium) was not significantly different between the two genotypes. In contrast, amphetamine-evoked release (1 microM) was significantly greater in the weaver mice than in controls. In both genotypes, release evoked by amphetamine was completely inhibited by cocaine, implicating the dopamine uptake carrier in this release process. These findings suggest that fundamental differences in dopamine release mechanisms exist between weaver and control mice and support the hypothesis that compensatory mechanisms may develop in neurons in response to dopamine deficits.
Simon
J R
JR
Department of Psychiatry, Indiana University School of Medicine, Indianapolis 46202-4887.
Yu
H
H
Richter
J A
JA
Vasko
M R
MR
Ghetti
B
B
D000661:Amphetamine / Q000494:pharmacology; D000818:Animals; D003042:Cocaine / Q000494:pharmacology; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism*; D004298:Dopamine / Q000378:metabolism*; D005838:Genotype; D006720:Homozygote; D066298:In Vitro Techniques; D051379:Mice; D008818:Mice, Neurologic Mutants; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D011188:Potassium / Q000494:pharmacology
D000661:Amphetamine; D003042:Cocaine; D011188:Potassium; D004298:Dopamine