Low-dose ethanol produces mixed effects on cortico-hippocampal theta rhythms and modifies hippocampal theta frequency through multiple mechanisms

Ethanol is one of the most widely used drugs - with many psychoactive effects, including anxiolysis. The deleterious effects on brain function and general health of chronic and high-level ethanol use are well-studied. However, the neurophysiology of acute low dose ethanol has not been systematically investigated. Here, we examined the effects of low dose (0.25 and 0.5 g/kg) ethanol on midline (prefrontal, cingulate and retrosplenial) cortical and hippocampal theta oscillations in freely moving rats. We also tested low dose ethanol on reticular-elicited and running-elicited hippocampal theta frequency and assessed the linear relationship of theta frequency to stimulation intensity and running speed, respectively. Low dose ethanol had mixed effects on cortical theta oscillations. It most reliably reduced theta frequency, produced a weak inverted-U effect on theta power, and had no detectable effect on cortico-hippocampal theta coherence. Ethanol dose-dependently decreased the y-intercept of the speed-theta frequency function without affecting the slope, but decreased the slope of the stimulation intensity-theta frequency function without affecting the y-intercept; thus decreasing theta frequency in both cases but through different mechanisms. We conclude low dose ethanol has weak but detectable effects on cortical and hippocampal theta oscillations. These effects may underlie positive cognitive and behavioural outcomes reported in the literature using low dose ethanol. The double dissociation of slope and y-intercept specific changes relating to different methods of hippocampal theta elicitation suggests that multiple mechanisms contribute to anxiolytic effects on theta and so hippocampal function.