Artigo Revisado por pares

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

2011; Elsevier BV; Volume: 131; Issue: 1-3 Linguagem: Inglês

10.1016/j.schres.2011.05.005

ISSN

1573-2509

Autores

Romina Mizrahi, Ofer Agid, Carol Borlido, Ivonne Suridjan, Pablo Rusjan, Sylvain Houle, Gary Remington, Alan A. Wilson, Shitij Kapur,

Tópico(s)

Neurological disorders and treatments

Resumo

Most antipsychotics are thought to have an effect on D2 and D3 receptors, although their D3, versus D2 binding has not been clearly established in vivo in humans. However, the development of [11C]-(+)-PHNO now permits the differentiation of antipsychotic activity on these two receptor subtypes. In this study we examined the effects of antipsychotics on D2 and D3 receptors by comparing [11C]-(+)-PHNO in D2-rich (caudate, CAU and putamen, PUT), mixed (ventral striatum) and D3-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-naïve state and then again after ~ 2.5 weeks of antipsychotic treatment (risperidone or olanzapine). Binding potential (non displaceable or BPND) was obtained to derive estimates of drug occupancy in the identified brain regions. Antipsychotic treatment was associated with the expected occupancies in the D2-rich regions; unexpectedly though, patients showed a higher, rather than the expected lower, [11C]-(+)-PHNO BPND in the GP and SN despite simultaneous evidence for ongoing D2 blockade in the other regions (CAU and PUT). In conclusion, patients treated with atypical antipsychotics demonstrated no evidence of D3 receptor occupancy, but instead possible D3 up-regulation following short-term treatment. The present findings add to a very limited body of evidence related to D3 binding in vivo. [11C]-(+)-PHNO offer new opportunities for exploring the potential therapeutic significance of the D3 receptor in schizophrenia and the action of antipsychotics.

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