Central catecholamine neurons, behavior and neuroleptic drugs: An analysis to understand the involvement of catecholamines in schizophrenia

Abstract

FOR MANY years central catecholamine (CA) neurons have been postulated to be involved in the cause of schizophrenia. Pharmacological evidence has e.g. indicated that antipsychotic drugs such as chlorpromazine, haloperidol and pimocide have the common property of blocking dopamine (DA) receptor sites in brain1 Furthermore, amphetamine, a CA releasing agent,2 can cause psychosis in man.3 In view of the pharmacological evidence many workers have favoured the involvement of DA neurons rather than noradrenaline (NA) neurons. This view has been strengthened by the discovery of new types of DA nerve terminals in the limbic cortex.4-7 On the other hand, STEIN (this meeting) has postulated that schizophrenia is caused by a degeneration of certain NA pathways. In support of this view he has presented evidence that dopamine+hydroxylase (DBH) activity is reduced in brains of schizophrenic patients. Furthermore, STEIN et aL8pg have demonstrated that with some electrode placements reward is dependent on NA release (see also (refs. (10)-(12)). A d e g eneration of NA pathways could thus lead to lack of reward which is one of the main symptoms in schizophrenia. Against this background of information it was found of interest to further analyse the role of DA and NA in, (1) unconditioned locomotor behavior especially after d-amphetamine administration in, (2) reward behavior (self-stimulation) and, in (3) conditioned avoidance behavior. In the latter case the studies demonstrate important interactions between CA and hormones which must be considered also when evaluating the role of CA in schizophrenia. Finally, the action of a new antipsychotic drug, clozapine,l3-15 on central DA neurons have been analysed. This drug appears to increase both DA and NA turnoverl” (FUXE, reported in (ref. (17)) but has the interesting property of lacking extrapyramidal side effects. In lower doses it also appears to increase DA turnover preferentially in the limbic system.18