Effects of anxiety-relieving drugs on unit discharges in hippocampus, reticular midbrain, and pre-optic area in the freely moving rat

The effects on unit discharges of various doses of the compounds chlordiazepoxide, meprobamate, sodium pentobarbital, and diazepam were studied in the unanesthetized, unrestrained rat. Recordings of action potentials were made simultaneously in hippocampus, pre-optic region, and the reticular formation of the midbrain. The doses of chlordiazepoxide were 5, 10, 20 and 40 mg/kg; 5, 10 and 20 mg/kg of sodium pentobarbital; 80, 100 and 120 mg/kg of meprobamate, and finally 5, 10 and 20 mg/kg of diazepam.

In the hippocampus, chlordiazepoxide depressed spontaneous activity at every dose used. The reduction ranged from 30 to 50%, but in no case was there inhibition of all discharges. Diazepam also had substantial depressing effects on the activity in this region of the brain. In contrast, sodium pentobarbital had relatively minor effects in the lower dose range, but significant depressing effects at the higher doses. Meprobamate also had comparatively small effects in the hippocampus.

In the pre-optic area, chlordiazepoxide and meprobamate depressed spontaneous activity at the higher dose range. There were small effects in the lower dose range. Sodium pentobarbital also had minor depressing effects at all doses. Diazepam caused less depression even at the higher doses than either chlordiazepoxide or meprobamate, and these effects were transient.

In the midbrain reticular formation, meprobamate caused substantial depression of spontaneous activity even at the lower doses. Sodium pentobarbital similarly depressed activity, but the onset of effect was less delayed than with meprobamate. Chlordiazepoxide at low doses caused less depression of reticular midbrain neurons than of hippocampal or pre-optic region ones. At high doses, the effect was similar to that of meprobamate.

The data suggest the possibility of a mode of action of chlordiazepoxide and diazepam which implicates the hippocampus, whereas in the case of sodium pentobarbital and meprobamate, the mode of action appears to implicate the midbrain reticular area. Such a view is based upon comparison of effects at low doses on spontaneous activity of the three regions investigated.