Presynaptic input regulates development of beta-adrenergic control of rat brain ornithine decarboxylase: effects of 6-hydroxydopamine or propranolol.
beta-Adrenergic control of ornithine decarboxylase (ODC) activity is exerted only during a critical period in central nervous system development, playing an important role in neurotransmitter modulation of cell replication and differentiation. The current study examines the effects of lesions caused by 6-hydroxydopamine administration to neonatal rats, or of gestational exposure to propranolol, on the subsequent development of the ODC response to beta-adrenergic stimulation elicited by an acute intracisternal challenge with isoproterenol. 6-Hydroxydopamine treatment severely attenuated the ability of isoproterenol to stimulate ODC in the cerebellum, a tissue that shows a postnatal peak of ODC reactivity. In contrast, much smaller effects were seen in the cerebral cortex, which has an earlier (pre/perinatal) peak of ODC, despite the fact that norepinephrine depletion was more persistent in the cortex. On the other hand, blockade of fetal beta-receptors by maternal propranolol infusions resulted in immediate postnatal attenuation of the ODC response in cerebral cortex, but not cerebellum. These data suggest that early exposure of beta-receptors to norepinephrine "programs" the subsequent efficiency of the receptor linkage to ODC during a critical ontogenetic period that occurs prenatally in the cerebral cortex and postnatally in the cerebellum.
Wagner
J P
JP
Department of Pharmacology, Duke University Medical Center, Durham, NC 27710.
Seidler
F J
FJ
Slotkin
T A
TA
D000375:Aging; D000818:Animals; D001921:Brain / Q000187:drug effects / Q000201:enzymology / Q000254:growth & development*; D002531:Cerebellum / Q000254:growth & development; D002540:Cerebral Cortex / Q000254:growth & development; D004298:Dopamine / Q000378:metabolism*; D009498:Neurotoxins / Q000494:pharmacology*; D009638:Norepinephrine / Q000378:metabolism*; D009955:Ornithine Decarboxylase / Q000378:metabolism*; D016627:Oxidopamine / Q000494:pharmacology*; D011433:Propranolol / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D011943:Receptors, Adrenergic, beta / Q000187:drug effects / Q000502:physiology*
D009498:Neurotoxins; D011943:Receptors, Adrenergic, beta; D016627:Oxidopamine; D011433:Propranolol; D009955:Ornithine Decarboxylase; D004298:Dopamine; D009638:Norepinephrine