[High dosage haloperidol reduces cataleptic response with increased noradrenaline metabolism in the rat brain areas]

The neurochemical background of clinical experiences that the patients receiving high dosage haloperidol showed no extrapyramidal side effects was investigated by using rats. Haloperidol at doses of 1, 2.5, 5, 7.5 and 10 mg/kg, ip caused a dose-dependent decrease in the duration of catalepsy. Haloperidol at a dose of 10 mg/kg induced catalepsy lasting only 20% of that by 1 mg/kg. Haloperidol decreased noradrenaline content in the frontal cortex and thalamus in a dose-dependent manner while 3-methoxy-4-hydroxyphenylglycol content showed a dose-dependent increase in the same brain areas. Thus, there is an inverse relationship between the duration of catalepsy and the ratio of 3-methoxy-4-hydroxyphenylglycol to noradrenaline in the frontal cortex or thalamus. In contrast, haloperidol caused a dose-dependent decrease in homovanillic acid and 3, 4-dihydroxyphenylacetic acid content in the striatum and mesolimbic area. These results indicate that noradrenergic hyperfunction in the frontal cortex or thalamus induced by high dosage haloperidol may reduce cataleptogenic effect of the drug via indirect stimulation of dopaminoceptive neuron in the striatum or mesolimbic area.