Background: Despite evidence showing persistent changes in N-methyl-D-aspartate (NMDA)-receptor function following ethanol (EtOH) exposure, the contribution of NMDA systems to the long-term neurophysiological consequences of adolescent EtOH exposure is unclear. The aims of this study were the following: (1) to determine whether adolescent EtOH exposure produces neurophysiological changes after a prolonged withdrawal period in adult rats and (2) to assess protracted alterations in neurophysiological responses to the NMDA antagonist MK-801 in adult rats exposed to EtOH during adolescence.
Methods: Adolescent male Wistar rats were exposed to EtOH vapor for 12 h/d for 5 weeks. The effects of MK-801 (0.0 to 0.1 mg/kg, intraperitoneally) on the electroencephalogram (EEG) and auditory event-related potentials (ERPs) were assessed after 8 weeks of abstinence from EtOH.
Results: Experiments in aim 1 revealed that adolescent EtOH exposure reduced EEG variability in the frontal cortex in the 4 to 6 Hz band but had no effect on cortical and hippocampal EEG power and ERPs. Experiments in aim 2 showed that MK-801 significantly reduced EEG power in the parietal cortex (4 to 6 Hz, 6 to 8 Hz, 8 to 16 Hz, 16 to 32 Hz) and hippocampus (16 to 32 Hz) and EEG variability in the parietal cortex (6 to 8 Hz, 16 to 32 Hz) following adolescent EtOH exposure. MK-801 produced a significant decrease in hippocampal EEG variability (4 to 6 Hz, 8 to 16 Hz, 16 to 32 Hz) in control, but not in EtOH-exposed rats. MK-801 reduced frontal P1 ERP amplitude and latency in response to the rare tone in EtOH-exposed rats compared to controls. In contrast, MK-801 significantly reduced P3 ERP amplitude and latency in control, but not in EtOH-exposed rats.
Conclusions: The effects of MK-801 on hippocampal EEG variability and P3 ERP amplitude and latency are significantly attenuated after a prolonged withdrawal period following adolescent EtOH exposure. However, the inhibitory effects of MK-801 on cortical and hippocampal EEG power were enhanced in rats exposed to EtOH during adolescence. Taken together, these data suggest protracted changes in NMDA systems following adolescent EtOH exposure.