Acute stimulation of ornithine decarboxylase in neonatal rat brain regions by nicotine: a central receptor-mediated process?
Nicotine exposure during development alters central nervous system structure and function. In the current study, we examined the acute effects of nicotine (3 mg/kg) on developing rat brain by monitoring ornithine decarboxylase (ODC), a marker for perturbed cell development; ODC controls polyamine biosynthesis and thus regulates cell differentiation. Three brain regions were selected that differ both in their timetables for maturation and in nicotinic receptor concentrations: midbrain + brainstem (earliest development, highest receptor concentration), forebrain (intermediate profiles) and cerebellum (latest development and lowest receptor concentration). Nicotine caused stimulation of ODC within 1 h after drug administration, an effect that displayed both age- and region-dependence corresponding to the development of central nicotinic receptors: effects appeared earliest and were largest in magnitude in midbrain + brainstem and forebrain, and appeared last and with smaller magnitude in the cerebellum. Central receptor involvement was confirmed at 8 days postpartum by demonstrating desensitization of the response after repeated nicotine administration, and by evoking equivalent effects with direct introduction of a small dose of nicotine into the central nervous system. Later in development, acute stimulation of ODC by nicotine became less selective, reflecting secondary actions mediated through systemic hypoxia caused by the drug; this conclusion was confirmed by the absence of desensitization after repeated nicotine administration, and by the failure of centrally administered nicotine to evoke a full stimulatory response. Nicotine-induced ischemia did not contribute to stimulation of ODC seen at the 1 h time point: pretreatment with chlorisondamine, a ganglionic nicotinic antagonist, failed to alter the central stimulatory response.(ABSTRACT TRUNCATED AT 250 WORDS)
Smith
W T
WT
Department of Pharmacology, Duke University Medical Center, Durham, NC 27710.
Seidler
F J
FJ
Slotkin
T A
TA
D000818:Animals; D000831:Animals, Newborn / Q000378:metabolism*; D001921:Brain / Q000187:drug effects* / Q000201:enzymology / Q000254:growth & development; D009538:Nicotine / Q000494:pharmacology*; D009955:Ornithine Decarboxylase / Q000187:drug effects*; D051381:Rats; D011919:Rats, Inbred Strains; D011978:Receptors, Nicotinic / Q000502:physiology*; D013997:Time Factors
D011978:Receptors, Nicotinic; D009538:Nicotine; D009955:Ornithine Decarboxylase