Similar effects of medial supramammillary or systemic injection of chlordiazepoxide on both theta frequency and fixed-interval responding

Abstract

The frequency of theta activity may be important for hippocampal function. Anxiolytic drugs reduce theta frequency and have behavioral effects that are similar to those of hippocampal lesions. The effect of the anxiolytic benzodiazepine chlordiazepoxide (CDP) on theta frequency is partially mediated by the medial supramammillary nucleus (mSuM), part of an ascending theta-activating system. Rats were trained on the hippocampal-sensitive fixed-interval 60-sec schedule (FI60). CDP (5 mg/kg i.p.) released responding suppressed by nonreward, seen as increased leverpressing, and reduced theta frequency concurrently. Microinfusion of CDP (20 μg in 0.5 μl saline) into mSuM had as large effects on both frequency and behavior. Other nuclei mediate the benzodiazepine reduction of theta frequency in the open field and the water maze. But the mSuM appears to be the major, if not sole, nucleus controlling theta frequency and, so, hippocampal-mediated behavioral inhibition in the FI60 lever task.