Does clozapine treat antipsychotic-induced behavioural supersensitivity through glutamate modulation within the striatum?

Prashant Tibrewal, Pramod C. Nair, Karen J. Gregory, Christopher J. Langmead, Sherry Kit Wa Chan, Tarun Bastiampillai

Research output: Contribution to journalComment/debate

2 Citations (Scopus)
11 Downloads (Pure)

Abstract

Behavioural supersensitivity may be a result of increased glutamate sensitivity of D2-MSN and reduced sensitivity to dopamine. We propose that clozapine may address behavioural supersensitivity by modulating glutamate activity which may partially explain its unique effectiveness in the setting of treatment resistant schizophrenia.

The mainstay of schizophrenia treatment is chronic antipsychotic medication to prevent relapse of a psychotic episode. These antidopaminergic drugs reduce D2 dopamine receptor-mediated transmission. It has been proposed that relapse rates following antipsychotic discontinuation may be due to withdrawal phenomenon rather than due to illness recurrence [1]. The leading hypothesis is chronic D2-receptor blockade produces compensatory changes leading to a state of dopamine supersensitivity (or behavioural supersensitivity) by potentiating D2-receptor density/function specifically in the striatum [2]. An alternate hypothesis is that increased glutamate but decreased dopamine sensitivity occurs during chronic antipsychotic treatment implying the role of the glutamatergic system [3]. There is also some scepticism on the existence of dopamine supersensitivity based on strict clinical observation
Original languageEnglish
Pages (from-to)1839-1842
Number of pages4
JournalMOLECULAR PSYCHIATRY
Volume28
Issue number5
Early online date17 Mar 2023
DOIs
Publication statusPublished - May 2023

Keywords

  • clozapine
  • antipsychotic medication
  • glutamate modulation
  • antidopaminergic
  • D2-MSN

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