Neurobiology of Supersensitive D₁ and D₂-Dopamine Receptors after 6-Hydroxydopamine Lesions

Abstract

Administration of L-DOPA to rats treated as neonates or as adults with 6-hydroxydopamine (6-OHDA; Breese and Traylor, 1970; Smith et al., 1973) results in enhanced behavioral responses (Breese, 1975). However, behavioral responses to L-DOPA differ depending on the age at which dopaminergic fibers are destroyed (Breese et al., 1984). For example, following L-DOPA, rats lesioned with 6-OHDA as neonates show self-biting and self-mutilation behavior, but rats treated as adults do not (Breese et al., 1984). In initial experiments, Breese et al. (1984) observed that cis flupentixol was more potent than haloperidol in antagonizing self-biting induced by L-DOPA in neonatally lesioned rats, suggesting that D₁-dopamine (DA) receptors were involved in the behavioral supersensitivity observed in rats whose DA-containing neurons were destroyed during development (Breese et al., 1984). The availability of agonists and antagonists with specificity for D₁-and D₂-DA receptors and animal models by which to study D₁-and D₂-DA receptor responses allowed us to test this hypothesis as well as to evaluate further the neurobiology of these receptor subtypes (Breese et al., 1985ab, 1986, 1987).