Effects of ethanol on muscarinic receptor-stimulated phosphoinositide metabolism during brain development

The pattern of muscarinic receptor-stimulated inositol metabolism during postnatal development has a striking resemblance with the curve of rat brain growth spurt. Therefore, the enhanced hydrolysis of membrane inositol lipids by cholinergic agonists during this period may have a relevant role in cell proliferation and differentiation. In this study we have investigated whether exposure to EtOH to rat pups during the brain growth spurt, known to cause a permanent microencephaly, would alter muscarinic receptor-stimulated inositol metabolism in cerebral cortex. Female Long-Evans rats were administered 4 g/kg of EtOH, in two doses of 2 g/kg, by gastric intubation from postnatal day 4 to day 10. This treatment did not have any effect on the pups' body weight as compared to an equally handled, sucrose-fed group of animals. Blood EtOH concentration in the pups during exposure ranged between 237 and 283 mg/dl. Muscarinic receptor-stimulated inositol metabolism was measured in cerebral cortex slices of control and EtOH-treated rats at days 4, 7, 10, 12, 20 and 45 of age. Carbachol-induced accumulation of [3H] inositol phosphates was reduced significantly in EtOH-exposed animals on day 7 and 10, but not at other ages. This decrease was not due to an alteration of muscarinic receptor density or affinity. Exposure to EtOH had no effect on phosphoinositide metabolism stimulated by norepinephrine, serotonin or histamine in cerebral cortex, whereas the effect of glutamate was increased. Similar results were observed in the hippocampus. An identical treatment with EtOH in adult rats did not cause alteration in any of the biochemical parameters of the cholinergic system measured.(ABSTRACT TRUNCATED AT 250 WORDS)