In vivo microdialysis studies of DA release in ventral strictum revealed higher basal levels of extracellular DA in mutant mice but similar inhibitory effects of PD 128907 in mutant and wildtype mice. In the gamma-butyrolactone (GEL) model of DA autoreceptor function, mutant and wild-type mice were identical with respect to striatal DA synthesis and its suppression by PD 128907. The putative D-3 receptor-selective agonist R(+)-trans-3,4,4a,10b-tetrahydro-4-propyl-2H,5H-(1)benzopyrano(4,3-b)-1,4-oxazin-9-ol (PD 128907) was equipotent at inhibiting the activity of both populations of midbrain DA neurons in the two groups of mice. The basal firing rates of DA neurons within both the substantia nigra and ventral tegmental area were not different in D-3 receptor mutant and wild-type mice. This possibility was tested with mice lacking the D-3 receptor as a result of gene targeting. However, many pharmacological studies have suggested an autoreceptor role for the DA D-3 receptor. Considerable evidence has indicated that these DA autoreceptors are of the D-2 subtype of DA receptors. Dopamine (DA) autoreceptors expressed along the somatodendritic extent of midbrain DA neurons modulate impulse activity, whereas those expressed at DA nerve terminals regulate both DA synthesis and release.
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