The selectively bred alcohol-preferring (P) and alcohol-nonpreferring (NP) rats have been shown to possess a number of behavioral and electrophysiological differences in response to alcohol. We sought to evaluate whether or not P and NP rats would respond differently to other sedative-hypnotic drugs related to ethanol. EEG recordings were conducted following systemic administration of the NMDA receptor antagonist MK 801 (0.1 mg/kg, ip) and the GABA/benzodiazepine receptor complex agonist diazepam (1.5 mg/kg, ip). Nine P and nine NP rats was implanted with bipolar stainless steel electrodes in the frontal cortex, the dorsal hippocampus, the ventral thalamus, and the anterior amygdala. In the vehicle condition, P rats showed significantly greater power of the EEG in the slow frequencies as compared with NP rats in the frontal cortex. Furthermore, P rats were found to have lower peak theta frequency (6-8 Hz) than NP rats in the frontal cortex, the dorsal hippocampus, and the ventral thalamus. MK 801 produced a significantly greater increase in the mean power of the EEG in NP rats in the 8-16 Hz than in P rats, whereas diazepam was found to decrease theta peak frequency (6-8 Hz), but more so in NP rats that in P rats. These data suggest that, in addition to differential responsiveness to alcohol, P and NP rats also differ in response to drugs that modify GABA and glutamate neurotransmission.