Regulation of dopaminergic neuron firing by heterogeneous dopamine autoreceptors in the substantia nigra pars compacta

Dopamine (DA) receptors generate many cellular signals and play various roles in locomotion, motivation, hormone production, and drug abuse. According to the location and expression types of the receptors in the brain, DA signals act in either stimulatory or inhibitory manners. Although DA autoreceptors in the substantia nigra pars compacta are known to regulate firing activity, the exact expression patterns and roles of DA autoreceptor types on the firing activity are highly debated. Therefore, we performed individual correlation studies between firing activity and receptor expression patterns using acutely isolated rat substantia nigra pars compacta DA neurons. When we performed single-cell RT-PCR experiments, D₁, D₂S, D₂L, D₃, and D₅ receptor mRNA were heterogeneously expressed in the order of D₂L > D₂S > D₃ > D ₅ > D₁. Stimulation of D₂ receptors with quinpirole suppressed spontaneous firing similarly among all neurons expressing mRNA solely for D₂S, D₂L, or D₃ receptors. However, quinpirole most strongly suppressed spontaneous firing in the neurons expressing mRNA for both D₂ and D₃ receptors. These data suggest that D₂S, D₂L, and D₃ receptors are able to equally suppress firing activity, but that D₂ and D ₃ receptors synergistically suppress firing. This diversity in DA autoreceptors could explain the various actions of DA in the brain.