Minor tranquillizers, stress and central catecholamine neurons

Abstract

The effects of chlordiazepoxide, diazepam and nitrazepam on central DA and NA neurons of non-stressed and stressed rats were studied using histochemical and biochemical analysis of DA and NA. Estimations of DA and NA turnover in various regions of the brain were obtained by studying the decrease in stored DA and NA following treatment with a tyrosine hydroxylase inhibitor (H44/68) or a DA-β-hydroxylase inhibitor (FLA63). Stress was induced by immobilization. (1) Stress increased NA turnover in all parts of the brain and the spinal cord. By biochemical methods it was shown that DA turnover in the telencephalon was significantly reduced. (2) By histochemical methods it was shown that chlordiazepoxide and diazepam decreased NA turnover in the cortex cerebri and cortex cerebelli and the hippocampal formation but did not do so to any significant extent in the hypothalamus or the lower brain stem. These results show that the benzodiazepine derivatives decrease the impulse activity in the NA neurons of the locus coeruleus which innervate all cortices of the brain. (3) Chlordiazepoxide and diazepam caused a small but significant decrease in DA turnover in ascending DA neurons to the neostriatum and the limbic forebrain indicating reduced impulse flow in these neurons. (4) Chlordiazepoxide, diazepam and nitrazepam caused a blockade of the stress-induced activation of NA neurons by decreasing nervous activity in these neurons. (5) Chlordiazepoxide and diazepam potentiated the stress-induced decrease in nervous activity in ascending DA neurons. Stress combined with these drugs therefore decreased DA turnover in the telencephalon in comparison with normal controls. In view of the role which the central NA and DA neurons probably play in behavioral and EEG arousal it seems that the decrease in nervous activity in DA and NA neurons produced by chlordiazepoxide and diazepam may be responsible for part of the pharmacological effects of these tranquillizers such as sedation and EEG slowing.