In this double-blind, placebo-controlled study, we examined the effects of subanesthetic doses of ketamine (an NMDA glutamate receptor antagonist) and thiopental (a GABA-A receptor agonist) on the event-related potential (ERP) correlates of deviant stimulus processing in 24 healthy adults. Participants completed three separate pharmacologic challenge sessions (ketamine, thiopental, saline) in a counterbalanced order. EEG data were recorded both before and during each challenge while participants performed a visual “oddball” task consisting of infrequent “target” and “novel” stimuli intermixed with frequent “standard” stimuli. We examined drug effects on the amplitude and latency of the P3(00) component of the ERP elicited by target (P3b) and novel stimuli (P3a), as well as the N2(00) and P2(00) components elicited by both targets and novels. Relative to placebo, both drugs reduced the amplitude of parietal P3b, and also tended to attenuate Target N2. Their effects on novelty processing were more differentiated. While both drugs reduced parietal P3a, this effect was greater for thiopental. Relative to placebo, ketamine also increased frontal P3a amplitude, shortened P3a latency, reduced N2, and enhanced P2 to novel stimuli.

The findings support the hypothesis that in healthy subjects intravenous ethanol administration has a concentration effect on pain tolerance but not on pain threshold. Additional studies are planned to further elucidate the mechanisms of ethanol's analgesic effects.