Effects of chronic prenatal ethanol exposure on cGMP content and glutamate release in the hippocampus of the neonatal guinea pig

The glutamate-N-methyl-D-aspartate (NMDA) receptor-nitric oxide synthase (NOS)-cGMP signal transduction system plays key neurotrophic and intercellular communication roles in the hippocampus. In the guinea pig, chronic prenatal ethanol exposure (CPEE), via maternal ethanol administration, suppresses the hippocampal glutamate-NMDA receptor-NOS pathway in the near-term fetus and decreases stimulated glutamate release in the hippocampus of young postnatal offspring, with no effect on NMDA receptor number or NOS activity. At present, the effect of CPEE on cGMP, a key second messenger of the glutamate signal transduction system, in the hippocampus is not known. The objective of this study was to test the hypothesis that CPEE suppresses the hippocampal glutamate signal transduction system in the neonatal guinea pig at the levels of cGMP content and glutamate release. Timed pregnant guinea pigs received chronic oral administration of 4 g ethanol/kg maternal body weight/day, isocaloric-sucrose/pair-feeding, or water treatment throughout gestation. CPEE decreased brain and hippocampal weights at postnatal day (PD) 1 and PD 5 (P<.05). CPEE did not affect basal, NMDA (1, 10, or 100 microM)-stimulated, or K(+) (15 or 30 mM)-stimulated cGMP content in transverse hippocampal slices at PD 1 or 5. At 60 mM K(+), however, CPEE decreased stimulated hippocampal cGMP content at PD 1 (P<.05) and increased stimulated cGMP content at PD 5 (P<.05). In transverse hippocampal slices, CPEE did not affect basal or K(+) (40 or 45 mM)-stimulated glutamate release at PD 1 or 5, or NMDA (50 microM)-stimulated glutamate release at PD 1, but did decrease NMDA (50 microM)-stimulated glutamate release at PD 5 (P<.05). The data demonstrate that the effects of CPEE on stimulated cGMP content and glutamate release in the hippocampus of the neonatal guinea pig are stimulating agent- and age-dependent.