DOPAMINE-CELL DEPOLARIZATION BLOCK AS A MODEL FOR THE THERAPEUTIC ACTIONS OF ANTIPSYCHOTIC-DRUGS

Antipsychotic drugs used in the treatment of schizophrenia have in com mon the property of being dopamine-receptor antagonists. However, the rapid timecourse of receptor blockade produced upon drug administratio n does not correlate with the emergence of clinical actions, which typ ically require weeks of treatment to become manifest. Studies in rats have shown that repeated antipsychotic drug treatment results in a del ayed inactivation of dopamine neuron firing in the midbrain due to dep olarization block. Furthermore, the therapeutic efficacy of antipsycho tic drugs in humans correlates with their ability to induce depolariza tion block of mesolimbic dopamine neurons, whereas their potential to produce extrapyramidal side effects correlates with their propensity f or inducing depolarization block in the nigrostriatal dopamine system. Therefore, dopamine-cell depolarization block is an effective model f or evaluating antipsychotic drug efficacy, and provides a potential me chanism to account for their therapeutic impact on a dysregulated dopa mine system.