Effects of diazepam and zolpidem on EEG beta frequencies are behavior-specific in rats

A pharmacological dissociation of the relation between electroencephalographic (EEG) activity and behavior has been described for the benzodiazepines. While a decrease in high frequency EEG activity is associated with a decrease in arousal in drug-free conditions, sedative benzodiazepines increase beta activity. Non-benzodiazepine GABA(A) receptor modulators can increase beta activity as well. To further study the relationship between rat behavior and EEG under GABA(A) receptor modulation, EEG effects of diazepam (2.5 mg/kg) and zolpidem (2.5 mg/kg) were studied during different behaviors. Both drugs modulate the GABA(A) receptor, albeit that zolpidem shows alpha(1) subunit selectivity while diazepam is non-selective. A detailed analysis of rat open field behavior was made with a distinction of 25 behavioral elements. The EEG was segmented according to each behavioral element and a corresponding power spectrum calculated. Both diazepam and zolpidem increased EEG beta frequencies, characteristic for the benzodiazepines. However, the beta and gamma increase was specific for active behavior and not for inactivity. Interestingly, diazepam and zolpidem seemed to amplify, rather than dissociate, the relation between behavior and the EEG. It is hypothesized that the large increase in beta-3/gamma activity caused by diazepam and zolpidem is a compensatory mechanism that allows for behavioral activation, despite pharmacologically induced sedation.