Exposure of Rats to Ethanol from Postnatal Days 4 to 8: Alterations of Cholinergic Neurochemistry in the Cerebral Cortex and Corpus Striatum at Day 20

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Abstract
Male and female rat pups were administered ethanol (3 g/kg/dose) twice daily by intragastric intubation between postnatal Day (PN) 4 and 8. Pups were maternally reared throughout the exposure period and until sacrifice on PN20. The consequences of this growth spurt exposure to ethanol were measured by an impact upon body growth, as well as upon specific growth parameters and cholinergic neurochemical factors within the cerebral cortex and corpus striatum. Specific endpoints included muscarinic receptor binding dynamics, acetylcholinesterase (AChE) and choline acetyltransferase (CAT) activities, regional wet weights, and subcellular protein content. In male pups, ethanol resulted in a significant enhancement of body weight gain and an increase in striatal but not cortical mass. Additionally, ethanol exposure resulted in a significant increase in striatal muscarinic receptor affinity, regardless of gender. This was accompanied by evidence of a significantly greater density of striatal muscarinic receptors in males versus females, regardless of treatment. Overall, the ethanol-associated effects are suggestive of a drug-induced developmental delay. Gender-specific, treatment-independent differences were also detected in the developing brain regions. Thus, regardless of treatment, cerebral cortical S1-level protein content was found to be significantly greater in males than in females. Furthermore, there were gender-based, significant differences in AChE activity within the striatum of control pups (males > females). Ethanol exposure resulted in a loss of this gender-based difference. We conclude that the cholinergic neurochemical development occurring in the striatum of the female rat brain between PN4 and 8 is exquisitely sensitive to ethanol-induced developmental delays which are not remediable by 12 subsequent days of maternal rearing in the absence of ethanol exposure.