Journal of Neuroscience, Vol 9, 125-133, Copyright © 1989 by Society for Neuroscience
Priming of D1-dopamine receptor responses: long-lasting behavioral supersensitivity to a D1-dopamine agonist following repeated administration to neonatal 6-OHDA-lesioned rats
H Criswell, RA Mueller and GR Breese
Biological Sciences Research Center, School of Medicine, University of North Carolina, Chapel Hill 27599.
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)
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