Effects of antipsychotics on D3 receptors: A clinical PET study in first episode antipsychotic naive patients with schizophrenia using [11C]-(+)-PHNO

Abstract Most antipsychotics are thought to have an effect on D 2 and D 3 receptors, although their D 3 , versus D 2 binding has not been clearly established in vivo in humans. However, the development of [ 11 C]-(+)-PHNO now permits the differentiation of antipsychotic activity on these two receptor subtypes. In this study we examined the effects of antipsychotics on D 2 and D 3 receptors by comparing [ 11 C]-(+)-PHNO in D 2 -rich (caudate, CAU and putamen, PUT), mixed (ventral striatum) and D 3 -rich (globus-pallidus, GP and substantia nigra, SN) regions before and after the initiation of antipsychotic medication. The investigation therefore represents a longitudinal within-subject follow-up design wherein antipsychotic-naive patients with schizophrenia spectrum disorders were first scanned in a drug-naive state and then again after ~ 2.5 weeks of antipsychotic treatment (risperidone or olanzapine). Binding potential (non displaceable or BP ND ) was obtained to derive estimates of drug occupancy in the identified brain regions. Antipsychotic treatment was associated with the expected occupancies in the D 2 -rich regions; unexpectedly though, patients showed a higher, rather than the expected lower, [ 11 C]-(+)-PHNO BP ND in the GP and SN despite simultaneous evidence for ongoing D 2 blockade in the other regions (CAU and PUT). In conclusion, patients treated with atypical antipsychotics demonstrated no evidence of D 3 receptor occupancy, but instead possible D 3 up-regulation following short-term treatment. The present findings add to a very limited body of evidence related to D 3 binding in vivo. [ 11 C]-(+)-PHNO offer new opportunities for exploring the potential therapeutic significance of the D 3 receptor in schizophrenia and the action of antipsychotics.