Ventral striatum activation by typical versus atypical neuroleptics in a fMRI paradigm with monetary incentive stimuli

Abstract

Atypical neuroleptics, unlike typical neuroleptics, lead to less severe blockage of the dopaminergic neurotransmission in the ventral striatum, the most important structure of the so-called mesolimbic dopaminergic reward system. The functional effects of this on motivation and drive have not been investigated up to now. Using functional magnetic resonance imaging (fMRI) and a motivational paradigm with a monetary incentive delay task, a study was carried out on right-handed schizophrenic inpatients taking typical neuroleptics (n=10, 2F, age 31.5±11.3 years, haloperidole, flupentixole, fluphenazine) or atypical neuroleptics (N=10, 4F, age 38.3±11.3 years, risperidone, olanzapine, amisulpride, aripiprazole). The patients on atypical neuroleptics demonstrated more activity in the ventral striatum due to gain vesus loss anticipation than did patients on typical neuroleptics (SVC-FWE: T=3.57, p=0.02, activated voxels: 11). This was the first demonstration in a cross sectional comparison that the restriction induced by atypical neuroleptics on the mesolimbic reward and motivation system is less severe than that induced by typical neuroleptics. This would explain, for example, the more minor degree of (affective) negative symptoms seen in patients taking atypical neuroleptics. Currently data is being evaluated from longitudinal sections made in a study of patients who were switched from a typical neuroleptic to an atypical agent on the basis of the fMRI paradigm described.