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
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 language | English |
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Pages (from-to) | 1839-1842 |
Number of pages | 4 |
Journal | MOLECULAR PSYCHIATRY |
Volume | 28 |
Issue number | 5 |
Early online date | 17 Mar 2023 |
DOIs |
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Publication status | Published - May 2023 |
Keywords
- clozapine
- antipsychotic medication
- glutamate modulation
- antidopaminergic
- D2-MSN