DOPAMINE-RECEPTOR SUPERSENSITIVITY

Dopamine (DA) receptor supersensitivity refers to the phenomenon of an enhanced physiological, behavioral or biochemical response to a DA agonist. Literature related to ontogeneric aspects of this process was reviewed. Neonatal 5-hydroxydopamine (6-OHDA) destruction of rat brain DA neurons produces overt sensitization to D-1 agonist-induced ord activity, overt sensitization of some D-2 agonist-induced stereotyped behaviors and latent sensitization of D-1 agonist-induced locomotor and some stereotyped behaviors. This last process is unmasked by repeated treatments with D-1 (homologous ''priming'') or D-2 (heterologous ''priming'') agonists. A seroionin (5-HT) neurotoxin (5,7-dihydroxytryptamine) and 5-HT2C receptor antagonist (mianserin) attenuate some enhanced behavioral effects of D-1 agonists, indicating that 5-HT neurochemical systems influence D-1 receptor sensitization. Unlike the relative absence of change in brain D-1 receptor number, DA D-2 receptor proliferation accompanies D-2 sensitization in neonatal 6-OHDA-lesioned rats. Robust D-2 receptor supersensitization can also be induced in intact rats by repeated treatments in ontogeny with the D-2 agonist quinpirole. In these rats quinpirole treatments produce vertical jumping at 3-5 wk after birth and subsequent enhanced quinpirole-induced antinociception and yawning. The latter is thought to represent D-3 receptor sensitization. Except for enhanced D-1 agonist-induced expression of c-fos, there are no changes in the receptor or receptor-mediated processes which account for receptor sensitization. Adaptive mechanisms by multiple ''in series'' neurons with different neurotransmitters may account for the phenomenon known as receptor supersensitivity.