Overview of D3 receptors

Similar to the D2 and D4 receptors, the D3 receptor inhibits cAMP accumulation through coupling to G proteins. In addition, the D3 receptor inhibits Ca2+ currents and promotes mitogenesis, probably via tyrosine phosphorylation and activation of mitogen-activated protein kinases (Sokoloff and Schwartz, 2003). 

The expression of the D3 receptor in the brain is, in general, several times lower than that of the D2 receptor however, the affinity of DA is higher for the D3 receptor than for the D2 receptor. 

In contrast to studies on Di and D2 receptors, due to the relative lack of selective D3 drugs the majority of studies on D3 receptor distribution have been performed with in situ hybridization rather than with receptor binding autoradiography. 

D3 receptors are characterized by their abundance in limbic areas, whereas the presence of these receptors in motor or other cortical areas is limited (Sokoloff et al., 1990). A report by Levesque et al. (1992), utilizing the D3 receptor agonist [3H] 7-OH-DPAT, showed that the highest number of D3 receptor binding sites could be found in the NAc, olfactory tubercle and archicerebellum. This report was confirmed by several studies on D3 mRNA, which demonstrated that the highest level of receptor transcript was present in the ventral striatal complex (NAc, olfactory tubercle and islands of Calleja), SN and archicerebellum (Bouthenet et al., 1991 Diaz et al., 1995). 

Detailed studies on the rat brain reported a wider distribution of the D3 mRNA. In particular, high density of the D3 transcript was detected in the medial mammillary 

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