[Adaptation to neuroleptic preparations and several ways of combatting it (experimental study)]

To study the possible mechanisms of the formation of secondary therapeutic resistance, the author carried out a chronic experiment on animals which were administered different doses of a neuroleptic (haloperidol) for 20 days. The neuroleptic effect of the drug was shown to significantly decrease following prolonged administration. It was found that upon the first administration of haloperidol mice developed marked catalepsy 2 hours after administration. In conditions of a prolonged administration of the drug its cataleptogenic action was observed to diminish by the 20th day. Diminution of catalepsy was explained by a decrease of the blocking effect of the neuroleptic on the dopamine system. Change in the function of dopamine receptors (zigzag administration of haloperidol or administration of the drug simultaneously with apomorphine) was found to restore the cataleptogenic properties of the neuroleptic. The data obtained were used in the treatment of 47 patients with paranoid schizophrenia who developed resistance to pharmacotherapy.