BACKGROUND: Reduced cortical inhibition mediated by GABA (gamma-aminobutyric acid) is reported in depression, anxiety disorders, and aging. A novel positive allosteric modulator that specifically targets the α5-GABA METHODS: We analyzed EEG in 10 freely moving rats at baseline and following injections of α5-PAM (GL-II-73) and diazepam. RESULTS: We showed that α5-PAM specifically decreased theta peak power, whereas diazepam shifted peak power from high to low theta while increasing beta and gamma power. EEG decomposition showed that these effects were periodic and corresponded to changes in theta oscillation event duration. CONCLUSIONS: Thus, our study shows that α5-PAM has robust and distinct EEG biomarkers in rodents, indicating that EEG could enable noninvasive monitoring of α5-PAM treatment efficacy.