KOSTRZEWA, R.M. Dopamine receptor supersensitivity. NEUROSCI BIOBEHAV REV 19(1) 1-17, 1995. -- Dopamine (DA) receptor supersensitivity refers to the phenomenon of an enhanced physiological, behavioral or biochemical response to a DA agonist. Literature related to ontogenetic aspects of this process was reviewed. Neonatal 6-hydroxydopamine (6-OHDA) destruction of rat brain DA neurons produces overt sensitization to D 1 agonist-induced oral 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 serotonin (5-HT) neurotoxin (5,7-dihydroxytryptamine) and 5-HT 2 C 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.