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THE DETERMINATION BY QUANTITATIVE HISTOCHEMISTRY OF THE EFFECT OF PHENOTHIAZINES ON BRAIN CYTOCHROME C OXIDASE ACTIVITY
1 Houston State Psychiatric Institute, Houston, Texas 77025
The Burstone method (1961) for the histochemical demonstration of cytochrome c oxidase was quantified and applied to the study of the effects of chlorpromazine and trifluoperazine on the activity of this enzyme in rat forebrain, hypothalamus, cerebellum and pons-medulla. Fresh frozen, 10-µ-thick sections from rat brain were incubated in a buffered medium containing p-aminodiphenylamine and 8-amino-1,2,3,4-tetrahydroquinoline. The colored oxidized product of cytochrome c oxidase activity was extracted with ethanol and the optical density determined. In one series of experiments the phenothiazine was added to the incubating medium. For 50% inhibition of cytochrome c oxidase the following average tissue concentrations of chlorpromazine were required: cerebellum, 20 mM; forebrain, 27 mM; pons-medulla, 42 mM. Trifluoperazine was required in higher concentrations: cerebellum, 38 mM; forebrain, 47 mM; ponsmedulla, greater than 70 mM. In another series the phenothiazine was given intraperitoneally, 100-200 mg/kg. No significant inhibition of the enzyme was noted. The tissue concentration in vivo of the drug was well below the tissue concentration in vitro associated with minimum enzyme inhibitions.
Submitted on June 23, 1965
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