Priming of D1-dopamine receptor responses: long-lasting behavioral supersensitivity to a D1-dopamine agonist following repeated administration to neonatal 6-OHDA-lesioned rats

摘要

The present study demonstrates that repeated administration of SKF- 38393, a D1-dopamine agonist, is necessary for maximal behavioral supersensitivity of D1-dopamine receptor responses in neonatal 6-OHDA- lesioned rats, confirming earlier work. This repeated administration of SKF-38393, which is referred to as priming of D1-dopamine receptor responses, resulted in a progressive increase in locomotor activity, as well as several other behaviors. This priming phenomenon lasted at least 6 months. Repeated administration of the D2-dopamine agonist LY- 171555 also increased behavioral responses to the D1-dopamine agonist. However, previous administration of a D2-dopamine agonist was not necessary for priming of D1-dopamine receptor responses, because D1- dopamine receptor priming could be produced in the presence of a D2- dopamine receptor antagonist. Blockade of D1-dopamine receptors with SCH-23390 prior to injection of SKF-38393 prevented the increasing responsiveness following repeated administration of this D1-dopamine agonist. Selective neonatal destruction of dopamine-containing neurons produced the same result as did destruction of catecholamine-containing neurons, indicating that the noradrenergic system is not involved in this phenomenon. Priming of D1-dopamine receptor responses by repeated administration of SKF-38393 was not observed in unlesioned controls or in rats that received catecholamine-depleting lesions as adults. Repeated administration of scopolamine also was able to prime behavioral responses to SKF-38393 in neonatal 6-OHDA-lesioned rats, indicating that endogenous release of dopamine can prime D1-dopamine receptor responses in neonatally lesioned rats. In addition, responses to indirect-acting agonists were enhanced in rats that had been primed with a D1-dopamine agonist when compared wit responses in unprimed animals.(ABSTRACT TRUNCATED AT 250 WORDS)