Chronic neuroleptic effects on dopamine neuron activity: a model for predicting therapeutic efficacy and side effects?

Abstract

The treatment for most psychotic patients was largely ineffectual and care primarily custodial until the discovery of the antipsychotic properties of chlorpromazine in 1953. Ten years later Carlsson and Lindqvist (1963) discovered that antipsychotic drugs (neuroleptics) exert a specific action on central catecholamine systems, and hypothesized that they produced their effects by blocking catecholamine receptors in catecholamine-innervated sites. They further posited that the receptor blockade resulted in an increase in catecholamine neuronal activity which was mediated through long-loop feedback pathways from forebrain regions innervated by catecholamine neurons (Carlsson and Lindqvist 1963). This concept was a major impetus behind the last two decades of research on the mode of action of neuroleptics. During this time the dopamine (DA) system has been the primary focus of attention and DA receptor blockers have continued to be the treatment of choice for the major symptoms of psychosis (Klein et al. 1980).