The effects of prenatal and/or early postnatal exposure to ethanol at high concentrations on N-methyl-D-aspartate (NMDA) receptor number and functioning in the weanling rat were examined. The binge-like exposure protocol was used in an animal model of acute ethanol effects at two critical periods of development. [3H]MK-801 binding parameters for the internal channel phencyclidine site were assessed in the presence of 10 microM glutamate and 10 microM glycine activation. Four treatment groups were included: (1) animals exposed to ethanol both prenatal and postnatal; (2) animals exposed only prenatal; (3) animals exposed early postnatal only; and (4) control animals with no exposure to ethanol. The results of the [3H]MK-801 binding experiments showed that both prenatal and postnatal exposure to ethanol resulted in a significant decrease in the density of NMDA receptors. In addition, data indicated an apparent increase in the percentage of high-affinity state (open channel state) relative to low-affinity state (close channel state) receptors in the ethanol-treated groups. These results show that both prenatal and postnatal ethanol exposure decrease NMDA receptor density in the cortex and hippocampus. The findings are consistent with previous observations by our laboratory and others that NMDA-mediated calcium influx is reduced in these regions, as well as in whole brain by prenatal ethanol exposure. It is suggested that after ethanol exposure, the remaining functional NMDA receptors might have altered sensitivity to coagonist activation with an increased probability of channel opening.
The effects of prenatal and/or early postnatal exposure to ethanol at high concentrations on N-methyl-D-aspartate (NMDA) receptor number and functioning in the weanling rat were examined. The binge-like exposure protocol was used in an animal model of acute ethanol effects at two critical periods of development. [3H]MK-801 binding parameters for the internal channel phencyclidine site were assessed in the presence of 10 microM glutamate and 10 microM glycine activation. Four treatment groups were included: (1) animals exposed to ethanol both prenatal and postnatal; (2) animals exposed only prenatal; (3) animals exposed early postnatal only; and (4) control animals with no exposure to ethanol. The results of the [3H]MK-801 binding experiments showed that both prenatal and postnatal exposure to ethanol resulted in a significant decrease in the density of NMDA receptors. In addition, data indicated an apparent increase in the percentage of high-affinity state (open channel state) relative to low-affinity state (close channel state) receptors in the ethanol-treated groups. These results show that both prenatal and postnatal ethanol exposure decrease NMDA receptor density in the cortex and hippocampus. The findings are consistent with previous observations by our laboratory and others that NMDA-mediated calcium influx is reduced in these regions, as well as in whole brain by prenatal ethanol exposure. It is suggested that after ethanol exposure, the remaining functional NMDA receptors might have altered sensitivity to coagonist activation with an increased probability of channel opening.
Greater persistence in extinction is observed following inconsistent reward compared to that observed following consistent reward, an effect termed the partial reinforcement extinction effect (PREE). We report three experiments in which the extinction rates of random partially reinforced (PRF) or continuously reinforced (CRF) infant rat pups were compared to the extinction rate of pups trained with an alternative and regular schedule of partial reinforcement, known as patterned single alternation (PSA). In PSA, subjects learn to alternate speed of responding in anticipation of the regular alternation of reward and nonreward trials in the straight alley runway. In Experiment 1, 17-day-old PSA subjects showed CRF-like extinction rates; whereas in Experiment 2, in which extinction was initiated early in training prior to the onset of the PSA discrimination, PSA subjects showed prolonged, PRF-like extinction curves. In contrast, 12-day-old pups in Experiment 3 showed no reward-schedule-related differences in extinction, despite differences in behavior during acquisition. These results prompt a modification of Amsel's (1962) model of discrimination learning, and suggest the existence of a dissociation between different types of reward-related expectancies in the younger subjects.
Early postnatal exposure to alcohol during early development produces deficits in learned persistence, as reflected in the partial reinforcement extinction effect (PREE) in weanling rats, and deficits memory-based learning, as shown by patterned single alternation (PSA) discrimination learning in preweanling rats. We report a partial replication of these effects using the intubation method instead of artificial rearing. Rat pups were intubated once per day with 4.5 g/kg/day alcohol in a milk-based diet or control diet on postnatal days (PNDs) 4 to 9, and then assessed for the PREE on PNDs 20 and 21 or PSA learning on PNDs 17 and 18. Compared with previous artificial rearing reports, the intubation method produced healthier and heavier pups, and yielded a consistently lower and less variable blood alcohol levels. Even with the lower alcohol levels, intubation with alcohol eliminated the PREE. Intubation with alcohol had a weaker but still detrimental effect on PSA learning. These results suggest that alcohol exposure during development can produce behavioral deficits in the absence of the more severe effects on brain and body growth typically associated with fetal alcohol syndrome.
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