Tolerance phenomena with neuroleptics catalepsy, apomorphine stereotypies and striatal dopamine metabolism in the rat after single and repeated administration of loxapine and haloperidol

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Abstract

The two neuroleptic drugs loxapine and haloperidol given in single doses to rats induce catalepsy, inhibit the stereotyped behaviour induced by apomorphine, and stimulate the metabolism of dopamine in the corpus striatum, as shown by an increased dopamine turnover rate, a lowering of the dopamine content and an accumulation of homovanillic acid. Upon repeated administration of 7–21 daily doses, the rats develop a very marked and fairly long-lasting tolerance toward the above actions of the drugs. The phenomena described appear to be a consequence of a loss of sensitivity of striatal neurons to the neuroleptics.

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    Part of this work was presented at the ‘2. Zentraleuropäisches Symposium für Neuropsychopharmakologie und Pharmakopsychiatrie, Split 30.9-2.10.1971’; Stille, G. and H. Lauener, Die Wirkung von Neuroleptika im chronischen pharmakologischen Experiment.

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