DA D1 Receptors and VCMs

In the 1980s Breese and colleagues demonstrated that a perinatal 6-hydroxydopamine (6-OHDA) lesion produced not only the expected DA denervation of neostriatum and nucleus accumbens but also life-long DA D1 receptor supersensitization of rats. Moreover, this effect was unaccompanied by an increase in DA D1 receptor number in the forebrain regions (Breese et al. 1985, 1987; Criswell et al. 1989). To better explore the association of DA Dt receptors with perioral movements, a series of studies was undertaken on rats so lesioned perinatally with 6-OHDA. These rats, in adulthood, were found to be 100-1,000 times more sensitive to Dt agonist-induced VCMs. Whereas 1- to 10-mg/kg dose of the Dj agonist SKF 38393 [(±)1-phenyl-2,3,4,5-tetrahydro-1H-3-benzazepine-7,8-diol] was needed to produce VCMs in intact rats (Rosengarten et al. 1983a), a 0.01- to 0.1-mg/kg dose was sufficient in producing VCMs in the 6-OHDA-lesioned rats (Kostrzewa and Gong 1991; Gong et al. 1994). The enhancement of Dt agonist-induced VCMs was evident as long as the 6-OHDA lesioning occurred within the first week after birth (Kostrzewa et al. 1993b) and as long as the 6-OHDA dose was sufficient to produce 98.5% DA depletion of neostriatum (Gong et al. 1993). Dt receptor sensitization was unaccompanied by a change in the 5max (i.e., number) and Kd (i.e., affinity) of D1 receptors, and there was no increase in the expression of high-affinity D1 receptors in neostriatum of those rats with enhancement of VCMs (Gong et al. 1994). Clearly, however, D1 receptor supersensitivity was manifest in 6-OHDA-lesioned rats in relation to vCm induction (Kostrzewa 1995; Kostrzewa et al. 1998, 1999, 2003, 2008a).

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