Chronic prenatal ethanol exposure impairs conditioned responding and enhances GABA release in the hippocampus of the adult guinea pig.
In this study, we assessed the effects of chronic prenatal ethanol exposure (CPEE) on spatial navigation in the water maze, conditioned responding using food-reinforced lever pressing, and amino acid neurotransmitter release from the hippocampus of the adult guinea pig. Pregnant guinea pigs were treated with ethanol (3 g/kg of maternal body weight/day), isocaloric-sucrose/pair-feeding, or water throughout gestation. Adult offspring were trained in two-lever operant chambers to respond for sucrose pellets, with one lever designated as the reward lever. There were no group differences in response acquisition or lever discrimination on a fixed-ratio 1 (FR-1) schedule. During extinction sessions, CPEE offspring maintained higher levels of responding on the previously reinforced lever, suggesting that CPEE increases perseveration and/or impairs response inhibition but does not affect operant responding for an appetitive reinforcer or the ability to discriminate rewarding from nonrewarding stimuli. In contrast, there was no effect of CPEE on performance in the water maze in the maternal ethanol regimen used in this study. CPEE did not alter electrically evoked glutamate or GABA release from hippocampal brain slices. However, when slices were tested after delivery of a tetanizing stimulation (five 5-s trains at 100 Hz), post-tetanic potentiation of electrically stimulated GABA release was greater in hippocampal slices obtained from CPEE offspring, whereas post-tetanic potentiation of electrically stimulated glutamate release was unaffected. These data suggest that conditioned learning is a sensitive behavioral measure of CPEE-induced brain injury. Increased activity-dependent potentiation of GABA release in the hippocampus may contribute to alterations in synaptic plasticity observed in CPEE offspring.
Department of Pharmacology and Toxicology, Queen's University, Kingston, Ontario, Canada.
M L
ML
Hayward
A E
AE
Martin
J F
JF
Brien
H C
HC
Dringenberg
M C
MC
Olmstead
J N
JN
Reynolds
D000818:Animals; D001692:Biological Transport; D002492:Central Nervous System Depressants / Q000494:pharmacology; D003213:Conditioning, Psychological / Q000187:drug effects; D000431:Ethanol / Q000494:pharmacology*; D005260:Female; D006168:Guinea Pigs; D006624:Hippocampus / Q000187:drug effects* / Q000378:metabolism; D018782:Maze Learning / Q000187:drug effects*; D018377:Neurotransmitter Agents / Q000378:metabolism; D011247:Pregnancy; D011256:Pregnancy Outcome; D011297:Prenatal Exposure Delayed Effects; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
D002492:Central Nervous System Depressants; D018377:Neurotransmitter Agents; D000431:Ethanol; D005680:gamma-Aminobutyric Acid