Adolescent rats exposed to ethanol showed deficits in water maze performance, had increased hug time, and failed to catch up with control rats during the weeks after the ethanol treatment period was over. Adult alcohol rats showed some behavioral dysfunction (increased latency and distance to find the hidden platform) but had problems swimming, and in the probe trial they performed as well as control rats. Also, in adult rats, ethanol-induced impairments were quickly reversed after the ethanol treatment was over, a finding that suggests impaired motor coordination more than a true learning deficit. Together, these data indicate that repeated ethanol treatment in adolescent rats, but not adult rats, show long-term impairments in maze performance.

The N-methyl-D-aspartate (NMDA) receptor plays an important role in developmental plasticity. Earlier, we have shown that blocking the NMDA receptor with the non-competitive antagonist phencyclidine (PCP), during a brief postnatal period, disrupts the water maze performance in young juvenile rats (starting at 25 days of age). We now show the long-term effects of postnatal phencyclidine exposure on spatial learning and memory. Male and female rats were exposed to PCP (1 and 5mg/kg) or saline, from postnatal days 5-15, and their performance in the Morris water maze (MWM) was tested both as adolescents (starting on postnatal day (PD) 35) and as adults (starting on postnatal day 60). Separate groups of adult male and female postnatal PCP-treated and saline-treated rats were sacrificed and saturation [3H]MK-801 binding experiments were carried out in their hippocampi and frontal cortices; hippocampus and frontal cortex have high densities of NMDA receptors and both regions are important in spatial learning and memory. Postnatal PCP administration disrupted the water maze performance both in adolescent and adult rats of both sexes. Adult male and female rats treated postnatally with PCP had increased maximal [3H]MK-801 binding in the hippocampus and frontal cortex compared to same-sex saline-treated controls. Taken together, repeated postnatal PCP (RPP) administration impaired the acquisition of spatial learning in adolescent and adult male and female rats, and this cognitive deficit was associated with increased [3H]MK-801 labeled NMDA receptor in the hippocampus and frontal cortex. These findings are consistent with the hypothesis that PCP treatment during the postnatal period produces deficits in the water maze performance by disrupting the developing glutamatergic system.

The N-methyl-D-aspartate (NMDA) receptor plays an important role in developmental plasticity. Previous studies have reported differences between the NMDA receptor-channel complex in the rat pup brain and the adult brain. In the present study, modulation of the NMDA channel complex as a function of age was measured to determine when the temporal switching of the NMDA receptor from the immature form to the adult mature form takes place. [(3)H]MK-801 binding was measured in the rat forebrain from postnatal day 1 to day 21. Our data suggest the presence of two types of NMDA receptors - an immature type and a mature type. The immature NMDA receptor, seen during the early postnatal period (day 1-day 14) is highly sensitive to spermidine, L-glutamate alone potentiates [(3)H]MK-801 binding, and glycine failed to potentiate an L-glutamate-induced increase in [(3)H]MK-801 binding. During the late postnatal period (after day 14) spermidine alone did not increase [(3)H]MK-801 binding as potently as it did during the early postnatal period, high-affinity [(3)H]MK-801 binding was not seen in the presence of L-glutamate alone, and L-glutamate and glycine or L-glutamate and spermidine or L-glutamate, glycine and spermidine together, significantly increased [(3)H]MK-801 binding in a manner similar to that reported in the adult brain. Together, the pharmacology of the NMDA receptor during the early postnatal period differs from the adult-like receptor seen during the late postnatal period, and that in rats the apparent switching of the NMDA receptor from the immature type to the mature type takes place after the second postnatal week.