[Influence of clonazepam, an anticonvulsant benzodiazepine drug, on the rat brain monoamine containing neurons especially on dopaminergic neurons (author's transl)]

Abstract

Clonazepam at two doses of 1 mg/kg i.p. significantly decreased 3, 4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) contents in the rat caudatus and cortex but not so in the olfactory tubercle, septum and hypothalamus. The drug decreased dopamine (DA) turnover rate in the caudatus, but did not inhibit tyrosine hydroxylase activity. The drug significantly enhanced stereotyped behavior induced by apomorphine and d-methamphetamine. Clonazepam enhanced apomorphine-induced decrease in striatal HVA, and cortical DOPAC and HVA contents, and d-methamphetamine-induced decrease in cortical DOPAC content. Reserpine pretreatment did not affect apomorphine-induced stereotypy and its enhancement with clonazepam. The drug did not activate adenylate cyclase nor DA-sensitive adenylate cyclase in the striatal homogenates and did not change cyclic AMP content in the caudatus. The drug inhibited phosphodiesterase activity in caudate and cortical homogenates but not in vivo. Clonazepam did not alter ChAc and AChE activities in the caudatus, 6 other cerebral regions and the spinal area. Clonazepam also decreased NE turnover in the caudatus and 5-HIAA contents in the brainstem area. These neurochemical and behavioral effects of clonazepam indicate probable postjunctional DA stimulation in the striatum and cortex of the type not linked with adenylate cyclase and phosphodiesterase but probably due to activation of inhibitory gamma-amino butyric acid (GABA) neurons on the strio-nigral pathway.