Effects of acute diazepam and clobazam on spontaneous locomotor activity and central amine metabolism in rats

Abstract

Following 2 h after a single injection of diazepam ( 10 mg/kg) although no effect was found on tyrosine hydroxylase in striatum (a region abundant in dopaminergic nerver endings), its activity in pons-medulla, a region known to be rich in noradrenergic cell bodies, was enhanced by 17%. Diazepman elevated the levels of norepinephrine and dopamine in several brain regions. However, it decreased the concentration of homovanillic acid and augmented that of 3,4-dihydroxyphenlacetic acid, an intraneuronal metabolite of dopamine, suggesting that this anti-anxiety agent reduced the neuronal release of dopamine and possible norepinephrine. The enhanced activity of tyrosine hydroxylase in pons-medulla appears to reflect a specific compensatory response to the postulated low levels of catecholamines in the synaptic clefts. Acute diazepam treatment decreased tryptophan hydroxylase activity and the endogenous levels of its substrate, tryptophan in mid-brain region; however, the levels of 5-hydroxytryptamine and its metabolite 5-hydroxyindoleacetic acid were markedly increased in hypothalamus, mid-brain and pons-medulla, suggesting that diazepam decreased the synthesis as well as the neuronal release of 5-hydroxytryptamine. Clobazam ( 10 mg/kg) which is a 1,5-benzodiazepine, failed to exert any significant effect on behavioural activity and catecholamine metabolism although like diazepam, it also enhanced the levels of 5-hydroxytryptamine and 5-hydroxyindoleacetic acid. It is suggested that whereas diazepam may exert its behavioural suppressant effect by reducing the turnover of actecholamine, its anxiolytic action may be related to decreased turnover of brain 5-HT.