title: Effects of chronic prenatal ethanol exposure on cGMP content and glutamate release in the hippocampus of the neonatal guinea pig.
abstract: 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.
authors.affiliation: Department of Pharmacology and Toxicology, Faculty of Health Sciences, Kingston, ON, Canada K7L 3N6.
authors.forename: N S
authors.initials: NS
authors.lastname: Butters
authors.forename: J N
authors.initials: JN
authors.lastname: Reynolds
authors.forename: J F
authors.initials: JF
authors.lastname: Brien
mesh_terms: D020268:Alcohol-Induced Disorders, Nervous System / Q000378:metabolism* / Q000503:physiopathology; D000818:Animals; D000831:Animals, Newborn; D001835:Body Weight / Q000187:drug effects / Q000502:physiology; D002908:Chronic Disease; D006152:Cyclic GMP / Q000378:metabolism*; D004195:Disease Models, Animal; D000431:Ethanol / Q000494:pharmacology*; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology; D005260:Female; D018698:Glutamic Acid / Q000378:metabolism*; D006168:Guinea Pigs; D006624:Hippocampus / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D008297:Male; D019001:Nitric Oxide Synthase / Q000187:drug effects / Q000378:metabolism; D009924:Organ Culture Techniques; D009929:Organ Size / Q000187:drug effects / Q000502:physiology; D011188:Potassium / Q000494:pharmacology; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D017729:Presynaptic Terminals / Q000187:drug effects* / Q000378:metabolism; D016194:Receptors, N-Methyl-D-Aspartate / Q000187:drug effects / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D009435:Synaptic Transmission / Q000187:drug effects* / Q000502:physiology
chemical_list: D018690:Excitatory Amino Acid Agonists; D016194:Receptors, N-Methyl-D-Aspartate; D000431:Ethanol; D018698:Glutamic Acid; D019001:Nitric Oxide Synthase; D006152:Cyclic GMP; D011188:Potassium