ENHANCED QUINPIROLE RESPONSE IN RATS LESIONED NEONATALLY WITH 5,7-DIHYDROXYTRYPTAMINE

The ontogenic destruction of dopamine (DA) neurons in rat brain is ass ociated with supersensitization of DA D-1, receptors. This effect is a ttenuated when rats are cotreated in ontogeny with the serotonin (5-HT ) neurotoxin, 5,7-dihydroxytryptamine (5,7-DHT). In an attempt to dete rmine whether 5-HT fibers might have a similar modulatory role on the sensitivity of the DA D-2 receptor complex, we pretreated rats with de sipramine HCl (20 mg/kg IP, base), 1 h before the DA neurotoxin, 6-hyd roxydopamine (6-OHDA; 134 mu g ICV, base) and/or 5,7-DHT (75 pg ICV) a nd/or vehicle. At about 3 months after birth dose-effect curves for qu inpirole-induced oral activity were constructed for each group of rats . We found that quinpirole, an agonist for the DA D-2 receptor complex , produced a dose-related increase in oral activity in all groups of r ats. After a 200 mu g/kg dose of quinpirole HCl, however, neonatal 5,7 -DHT-lesioned rats had a peak oral response of 54.4 +/- 5.1 (mean and SEM) vs. 22.6 +/- 4.8 for control rats (p < 0.01). In neonatal 6-OHDA- lesioned rats this dose of quinpirole increased oral activity to 36.8 +/- 5.8 oral movements (p < 0.05 vs. control). In rats lesioned with b oth 5,7-DHT and 6-OHDA, the oral response was not different from contr ol. The enhanced oral response to quinpirole in 5,7-DHT-lesioned rats was attenuated by spiperone, an antagonist for the DA D-2 receptor com plex. These findings are believed to be the first to demonstrate that receptors of the DA D-2 complex become sensitized after ontogenic inju ry to 5-HT fibers. This effect is opposite to the attenuated sensitivi ty of DA D-1 receptors in rats with a similar 5-HT lesion.