Wistar-Kyoto (WKY) rats, a model of treatment-resistant depression, show increased REM sleep, fragmented sleep-wake patterns, and higher EEG delta power during non-REM sleep compared to Sprague-Dawley (SD) rats. Ketamine suppressed REM sleep and increased EEG gamma power during wakefulness in both strains, but the gamma increase was nearly twice as large in WKY rats. Ketamine also increased beta oscillations only in WKY rats. Plasma concentrations of ketamine and its metabolites were similar in both strains, suggesting the differences are not due to metabolism. These findings support acute REM sleep suppression as a measure of antidepressant responsiveness.
Drug discrimination procedures in rats confirm that hallucinogenic effects of psychedelics like psilocybin, LSD, DMT, and 5-MeO-DMT are mediated primarily by 5-HT2A and 5-HT1A receptors. Plasma levels of psilocin required for generalization in rats (5–52 ng/mL) overlapped with human perceptual effects, while DMT and LSD needed higher exposures in rats than in humans. The duration of drug-lever generalization followed LSD > psilocybin > 5-MeO-DMT ≥ DMT, matching clinical experience. LSD showed a disconnect between plasma exposure and generalization, similar to clinical findings. These results support the translational value of drug discrimination assays for studying psychedelics.