Electrophysiological effects of dizocilpine (MK-801) in adult rats exposed to ethanol during adolescence.
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.
Criado
José R
JR
Department of Molecular and Experimental Medicine, The Scripps Research Institute, La Jolla, California 92037, USA.
Wills
Derek N
DN
Walker
Brendan M
BM
Ehlers
Cindy L
CL
D000818:Animals; D001835:Body Weight / Q000187:drug effects; D002492:Central Nervous System Depressants / Q000494:pharmacology*; D002540:Cerebral Cortex / Q000187:drug effects*; D016291:Dizocilpine Maleate / Q000494:pharmacology*; D004569:Electroencephalography; D000431:Ethanol / Q000097:blood / Q000494:pharmacology*; D005072:Evoked Potentials, Auditory / Q000187:drug effects*; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors / Q000187:drug effects*; D013997:Time Factors
D002492:Central Nervous System Depressants; D016194:Receptors, N-Methyl-D-Aspartate; D000431:Ethanol; D016291:Dizocilpine Maleate