Abstract
Background: Antipsychotic drugs are commonly used for various neuropsychiatric disorders, such as psychotic disorders, mood disorders, and neuropsychiatric symptoms in dementia. Their mechanism of action is thought to be by modulation of neurotransmitter activity in the brain, mainly dopamine. It has been suggested that antipsychotic drugs may also exert anti-inflammatory properties. This study aimed to examine whether the modulating effect of antipsychotic drugs on neurotransmitters attenuates the inflammatory response of microglia cells. Methods: Levels of interleukin 6 (IL-6) were measured following activation of microglia cultures with lipopolysaccharides and treatment with antipsychotic drugs (risperidone, haloperidol, and clozapine), neurotransmitters (dopamine, serotonin, and acetylcholine), or a combination of dopamine and either haloperidol or clozapine. Results: Haloperidol and clozapine decreased IL-6 secretion by microglia cells when treated at a concentration of 10-5M. Interestingly, dopamine at a concentration of 1 μM increased IL-6 secretion by the microglia cells, while a concentration of 100 μM decreased it. The combination of dopamine (from 0.001 μM to 100 μM) with either haloperidol (10-5M or 10-8M) or clozapine (10-5M or 10-7M) attenuated IL-6 secretion in a bell-shaped curve with a peak at 1 μM. High concentrations of both haloperidol and clozapine decreased IL-6 secretion, while low concentrations modestly increased IL-6 levels. Conclusions: Our findings support anti-inflammatory properties of antipsychotic drugs, and suggest that their action is mediated via the inhibition of dopaminergic activity in microglia cells. The bell-shaped curve of IL-6 secretion by microglia might suggest the presence of an “optimal zone” of operation for these cells that is mediated by dopamine.
Withdrawal versus continuation of chronic antipsychotic drugs for behavioural and neuropsychiatric symptoms in elderly patients with dementia
