[Effect of varying the dose of haloperidol during its prolonged administration on the development of tolerance and hypersensitivity in dopamine receptors].

It has been shown in experiments on male mice that prolonged administration (for 20 days) of haloperidol in doses of 0.1, 1.0, 5.0 and 10.00 mg/kg produced an increase in the tolerance to thecataleptogenic effect at the end of administration and a rise in 3H-spiroperidole binding with striatum membranes on the 5th day after discontinuation of the neuroleptic, which attests to an increase in the sensitivity of dopamine receptors. Variation of haloperidol dose every other three days during 20 days of drug administration (1.0--0.1 ... 1.0 mg/kg and 1.0--10.00 ... 1.0 mg/kg) eliminated the manifestations of tolerance and hypersensitivity of dopamine receptors. It is assumed that variation of the neuroleptic dose during prolonged administration prevents the development of extrapyramidal disorders of the hyperkinetic type.