Priming of D1-dopamine receptor responses: long-lasting behavioral supersensitivity to a D1-dopamine agonist following repeated administration to neonatal 6-OHDA-lesioned rats.
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)
Criswell
H
H
Biological Sciences Research Center, School of Medicine, University of North Carolina, Chapel Hill 27599.
Mueller
R A
RA
Breese
G R
GR
D015647:2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine; D000818:Animals; D000831:Animals, Newborn / Q000502:physiology; D001522:Behavior, Animal / Q000187:drug effects* / Q000502:physiology; D001552:Benzazepines / Q000494:pharmacology*; D004298:Dopamine / Q000378:metabolism / Q000502:physiology; D004777:Environment; D005260:Female; D006892:Hydroxydopamines / Q000494:pharmacology; D008297:Male; D008845:Microinjections; D009714:Nucleus Accumbens / Q000502:physiology; D016627:Oxidopamine; D051381:Rats; D011919:Rats, Inbred Strains; D011954:Receptors, Dopamine / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D017447:Receptors, Dopamine D1; D017448:Receptors, Dopamine D2; D013997:Time Factors
D001552:Benzazepines; D006892:Hydroxydopamines; D011954:Receptors, Dopamine; D017447:Receptors, Dopamine D1; D017448:Receptors, Dopamine D2; D015647:2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine; D016627:Oxidopamine; D004298:Dopamine