A single day of ethanol exposure during development has persistent effects on bi-directional plasticity, N-methyl-D-aspartate receptor function and ethanol sensitivity.
To determine factors that contribute to the learning deficits observed in individuals with fetal alcohol syndrome, we examined the effects of early postnatal ethanol exposure on forms of synaptic plasticity thought to underlie memory. Treatment of rat pups with ethanol on postnatal day 7 impaired the induction of N-methyl-D-aspartate receptor-dependent long-term potentiation and abolished homosynaptic long-term depression in the CA1 region of hippocampal slices prepared at postnatal day 30. An N-methyl-D-aspartate receptor-independent form of long-term potentiation induced by very high frequency stimulation could be induced in slices from ethanol-treated rats. Defects in long-term depression correlated with a diminished contribution of ifenprodil-sensitive N-methyl-D-aspartate receptors to synaptic transmission and defects in a spontaneous alternation behavioral task. Rats exposed to ethanol on postnatal day 7 also exhibited diminished sensitivity of synaptic N-methyl-D-aspartate receptors to block by ethanol at postnatal day 30 and decreased behavioral sedation to systemic ethanol injections. These results indicate that changes in synaptic plasticity and N-methyl-D-aspartate receptor function are likely to provide a neural substrate for the cognitive and behavioral changes that follow developmental ethanol exposure.
Izumi
Y
Y
Department of Psychiatry, Washington University School of Medicine, 660 South Euclid Avenue, St. Louis, MO 63110, USA. zorumskc@psychiatry.wustl.edu
Kitabayashi
R
R
Funatsu
M
M
Izumi
M
M
Yuede
C
C
Hartman
R E
RE
Wozniak
D F
DF
Zorumski
C F
CF
D000818:Animals; D000831:Animals, Newborn / Q000254:growth & development / Q000502:physiology*; D001522:Behavior, Animal / Q000187:drug effects; D004334:Drug Administration Schedule; D004351:Drug Resistance; D000431:Ethanol / Q000008:administration & dosage* / Q000037:antagonists & inhibitors / Q000494:pharmacology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects; D006993:Hypnotics and Sedatives / Q000037:antagonists & inhibitors; D007279:Injections, Subcutaneous; D007858:Learning / Q000187:drug effects; D009473:Neuronal Plasticity / Q000187:drug effects*; D010880:Piperidines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D016194:Receptors, N-Methyl-D-Aspartate / Q000187:drug effects / Q000502:physiology*; D013569:Synapses / Q000502:physiology*; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology
D018691:Excitatory Amino Acid Antagonists; D006993:Hypnotics and Sedatives; D010880:Piperidines; D016194:Receptors, N-Methyl-D-Aspartate; D000431:Ethanol; C010739:ifenprodil