Augmented sensitivity of D1-dopamine receptors in lateral but not medial striatum after 6-hydroxydopamine-induced lesions in the neonatal rat.
Lesioning of neonatal rats with the neurotoxin 6-hydroxydopamine (6-OHDA) reduced striatal dopamine (DA) levels to 3% of control levels and produced marked increases in the behavioral effects of the selective D1-DA receptor agonist SKF-38393 in these animals when tested as adults. However, no differences were observed, either in basal or D1-DA-stimulated striatal cAMP formation or in forskolin-stimulated or GTP-stimulated cAMP production, between control and lesioned animals. C-fos-like immunoreactivity after SKF-38393 was significantly greater in dorsolateral vs. ventromedial aspects of the striatum in lesioned animals. Like the c-fos response, augmented electrophysiological responsiveness to SKF-38393 occurred in lesioned rats in lateral, but not medial, portions of the striatum. No differences were found in nucleus accumbens in sensitivity to SKF-38393 between control and lesioned rats. Although autoradiographic determination of D1-DA receptor binding throughout the striatum and nucleus accumbens revealed no differences between unlesioned and lesioned rats, tyrosine hydroxylase-like immunoreactivity was reduced with a regional distribution inversely related to c-fos-like immunohistochemical expression. These findings demonstrate that regionally enhanced electrophysiological sensitivity of striatal neurons to D1-DA receptor agonists after neonatal 6-OHDA-induced lesions is associated with regional changes in c-fos-like immunoreactivity and tyrosine hydroxylase-like immunohistochemistry, but not with changes in D1-DA receptor autoradiography or D1-DA-stimulated adenylyl cyclase activity. Such regional consequences of 6-OHDA-induced lesions in neonates may contribute to the unique behavioral patterns observed when these rats are challenged with L-dopa or D1-DA agonists as adults.
Department of Psychiatry, University of North Carolina, School of Medicine, Chapel Hill.
P E
PE
Simson
K B
KB
Johnson
H A
HA
Jurevics
H E
HE
Criswell
T C
TC
Napier
G E
GE
Duncan
R A
RA
Mueller
G R
GR
Breese
D015647:2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine / Q000494:pharmacology; D000262:Adenylyl Cyclases / Q000032:analysis; D000818:Animals; D000831:Animals, Newborn / Q000502:physiology; D001345:Autoradiography; D003342:Corpus Striatum / Q000187:drug effects*; D005260:Female; D006160:Guanosine Triphosphate / Q000494:pharmacology; D007980:Levodopa / Q000494:pharmacology; D009714:Nucleus Accumbens / Q000187:drug effects; D016627:Oxidopamine; D011247:Pregnancy; D016760:Proto-Oncogene Proteins c-fos / Q000032:analysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D017447:Receptors, Dopamine D1 / Q000032:analysis / Q000187:drug effects*; D014446:Tyrosine 3-Monooxygenase / Q000032:analysis
D016760:Proto-Oncogene Proteins c-fos; D017447:Receptors, Dopamine D1; D007980:Levodopa; D015647:2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine; D006160:Guanosine Triphosphate; D016627:Oxidopamine; D014446:Tyrosine 3-Monooxygenase; D000262:Adenylyl Cyclases