Abstract：
:The effects of the dopamine D(3) receptor, a putative autoreceptor, have been investigated by comparing behavioral and neurochemical properties of wild-type mice and mice with a genetic deletion of the D(3) receptor. The D(3) knock-out mice were modestly hyper-responsive to a novel environment relative to wild-type mice, and, consistent with this, quantitative in vivo microdialysis revealed elevated striatal dopamine extracellular levels. The dynamic actions of autoreceptors on electrically evoked dopamine release were examined in striatal brain slices from these animals and monitored with fast scan cyclic voltammetry at carbon-fiber microelectrodes. Quinpirole, a dopamine receptor agonist with potency at both D(2) and D(3) receptors, inhibited evoked dopamine in a dose-dependent manner with a slightly higher dose required in the knock-out animals (EC(50) of 60+/-10 nM in wild-type animals and 130+/-40 in D(3) knock-out animals; both curves had a Hill slope near 2). Dopamine synthesis inhibition with alpha-methyl-p-tyrosine caused released dopamine levels to decrease in each genotype. However, regulation of secretion by autoreceptors was still operant. Dose-response curves to quinpirole were unchanged in D(3) knock-out tissue, but secretion-regulated release exhibited a Hill slope decreased to 1 in the wild-type animals. In both genotypes, similar quinpirole-evoked increases in uptake rate were evident following synthesis inhibition. These data are consistent with the D(3) receptor having a small but significant role as a dopamine autoreceptor that partially regulates secretion, but not synthesis, in the caudate-putamen.
journal_name
Neurosciencejournal_title
Neuroscienceauthors
Joseph JD,Wang YM,Miles PR,Budygin EA,Picetti R,Gainetdinov RR,Caron MG,Wightman RMdoi
10.1016/s0306-4522(02)00067-2keywords:
subject
Has Abstractpub_date
2002-01-01 00:00:00pages
39-49issue
1eissn
0306-4522issn
1873-7544pii
S0306452202000672journal_volume
112pub_type
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