Enhanced Quinpirole Response in Rats Lesioned Neonatally With 5,7-Dihydroxytryptamine

Document Type

Article

Publication Date

1-1-1995

Description

The ontogenic destruction of dopamine (DA) neurons in rat brain is associated with supersensitization of DA D1 receptors. This effect is attenuated when rats are cotreated in ontogeny with the serotonin (5-HT) neurotoxin, 5,7-dihydroxytryptamine (5,7-DHT). In an attempt to determine whether 5-HT fibers might have a similar modulatory role on the sensitivity of the DA D2 receptor complex, we pretreated rats with desipramine HCl (20 mg/kg IP, base), 1 h before the DA neurotoxin, 6-hydroxydopamine (6-OHDA; 134 μg ICV, base) and/or 5,7-DHT (75 μg ICV) and/or vehicle. At about 3 months after birth dose-effect curves for quinpirole-induced oral activity were constructed for each group of rats. We found that quinpirole, an agonist for the DA D2 receptor complex, produced a dose-related increase in oral activity in all groups of rats. After a 200 μg/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 both 5,7-DHT and 6-OHDA, the oral response was not different from control. The enhanced oral response to quinpirole in 5,7-DHT-lesioned rats was attenuated by spiperone, an antagonist for the DA D2 receptor complex. These findings are believed to be the first to demonstrate that receptors of the DA D2 complex become sensitized after ontogenic injury to 5-HT fibers. This effect is opposite to the attenuated sensitivity of DA D1 receptors in rats with a similar 5-HT lesion.

Link to Full Text

Share

COinS