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Hippocampal cholinergic alterations and related behavioral deficits after early exposure to phenobarbital

Authors
Journal
Brain Research Bulletin
0361-9230
Publisher
Elsevier
Publication Date
Volume
29
Issue
1
Identifiers
DOI: 10.1016/0361-9230(92)90002-f
Keywords
  • Choline Acetyltransferase Early Exposure Hippocampus Inositol Phosphate Morris Water Maze Muscarinic
Disciplines
  • Chemistry
  • Medicine

Abstract

Abstract Mice were exposed to phenobarbital(PhB) prenatally and neonatally. Prenatal exposure was accomplished by feeding the mother PhB (3 g/kg milled food) on gestation days 9–18. Neonatal exposure was accomplished by daily injections of 50 mg/kg sodium PhB directly to the pups on days 2–21. Long-term biochemical alterations in the pre- and postsynaptic septohippocampal system, as well as related behavioral deficits, were assessed in the treated animals. Significant increase in B max values for binding of [ 3H]QNB to muscarinic cholinergic receptors was obtained on both ages 22 and 50 in prenatally (40–90%, respectively, p < 0.001) and neonatally exposed (58–89%, p < 0.001) mice whereas K d remained normal. Similarly, a significant increase of inositol phosphate (IP) formation in response to carbachol was found after both prenatal and neonatal exposure to PhB ( p < 0.05). No alterations in choline acetyltransferase (ChAT) activity were observed in the prenatally or neonatally treated animals. The early exposed mice showed deficits in the performance in Morris water maze, a behavior related to the septohippocampal pathway. The results suggest that early exposure to PhB induces alterations in postsynaptic components of the hippocampal cholinergic system and concomitantly to impairment in hippocampus-related behavior.

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