Effects of m-chlorophenylpiperazine on receptor binding and brain metabolism of monoamines in rats.
m-Chlorophenylpiperazine (mCPP) was studied for its ability to displace the binding of (3)H-ligands for monoamines to brain membranes and its effect on monoamine metabolism in various brain areas of the rat. mCPP displaced (3)H-serotonin binding to cortex membranes (Ki = 10(-7) M) but had virtually no effect on (3)H-spiroperidol binding to striatal membranes used as ligand for dopamine receptors (Ki > 10(-5) M). mCPP showed Ki values very similar to those of noradrenaline in displacing the binding of (3)H-WB 4101 (2-2,6-dimethoxy-phenoxy-ethylaminomethylbenzodioxan) and (3)H-DHA ((3)H-dihydroalprenolol), used as ligands for alpha(1) and beta adrenergic receptors respectively. At 0.3 and 1 mg/kg, mCPP preferentially reduced serotonin metabolism (decrease of 5-hydroxy-indoleacetic acid level) in various brain areas but at 3 and 10 mg/kg it raised homovanillic levels in the striatum and nucleus accumbens and 3-methoxy-4-hydroxyphenylethylene glycol sulphate levels in the brain as well. The data are compatible with the hypothesis that at lower doses mCPP preferentially acts by mimicking the action of serotonin on postsynaptic receptors. It is suggested that the effects on dopamine metabolism observed with higher doses might be mediated by the action of mCPP on brain serotonin, whereas direct action on central noradrenaline-containing neurons could contribute to the increase of noradrenaline metabolism.
Invernizzi
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Istituto di Ricerche Farmacologiche, M. Negri, Via Eritrea, 62-20157 Milan, Italy.
Cotecchia
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De Blasi
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Mennini
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Pataccini
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Samanin
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