Understanding the Therapeutic Action of Antipsychotics: From Molecular to Cellular Targets With Focus on the Islands of Calleja

Overview

Journal Int J Neuropsychopharmacol

Publisher Oxford University Press

Specialty Psychiatry

Date 2024 Apr 17

PMID 38629703

Authors

Merve Direktor

Peter Gass

Dragos Inta

Affiliations

Soon will be listed here.

Abstract

The understanding of the pathophysiology of schizophrenia as well as the mechanisms of action of antipsychotic drugs remains a challenge for psychiatry. The demonstration of the therapeutic efficacy of several new atypical drugs targeting multiple different receptors, apart from the classical dopamine D2 receptor as initially postulated unique antipsychotic target, complicated even more conceptualization efforts. Here we discuss results suggesting a main role of the islands of Calleja, still poorly studied GABAergic granule cell clusters in the ventral striatum, as cellular targets of several innovative atypical antipsychotics (clozapine, cariprazine, and xanomeline/emraclidine) effective in treating also negative symptoms of schizophrenia. We will emphasize the potential role of dopamine D3 and M4 muscarinic acetylcholine receptor expressed at the highest level by the islands of Calleja, as well as their involvement in schizophrenia-associated neurocircuitries. Finally, we will discuss the implications of new data showing ongoing adult neurogenesis of the islands of Calleja as a very promising antipsychotic target linking long-life neurodevelopment and dopaminergic dysfunction in the striatum.

Citing Articles

Understanding the Therapeutic Action of Antipsychotics: Not yet Beyond Striatal Dopamine? A Comment on Direktor et al. (2024).

Reynolds G Int J Neuropsychopharmacol. 2024; 27(7).

PMID: 38955467 PMC: 11237989. DOI: 10.1093/ijnp/pyae028.

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