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Antipsychotics increase vesicular glutamate transporter 2 (VGLUT2) expression in thalamolimbic pathways
Larissa Moutsimilli1, Severine Farley, Marie-Anne El Khoury
1INSERM U513, 8 rue du General Sarrail, Créteil 94010, France.
Neuropharmacology
|December 25, 2007
Summary
Antipsychotic drugs, unlike antidepressants, increase vesicular glutamate transporter 2 (VGLUT2) mRNA in specific thalamic nuclei. This suggests VGLUT2 may indicate antipsychotic activity and thalamo-limbic pathways could be a novel drug target.
Area of Science:
- Neuroscience
- Pharmacology
- Molecular Biology
Background:
- Vesicular-glutamate-transporters (VGLUT1 and VGLUT2) identify glutamatergic neurons.
- Distinct expression patterns define VGLUT1-positive cortical and VGLUT2-positive subcortical systems.
- Increased VGLUT1 expression is a known marker for antidepressant activity.
Purpose of the Study:
- To investigate the effects of various psychotropic drugs on VGLUT2 mRNA and protein expression in the brain.
- To determine if VGLUT2 expression changes correlate with antipsychotic or antidepressant activity.
- To explore the role of thalamo-limbic glutamatergic pathways in psychotropic drug action.
Main Methods:
- Assessed VGLUT2 mRNA and protein expression in response to different psychotropic drugs.
- Utilized techniques to measure gene and protein levels in specific brain regions.
- Compared effects of typical antipsychotics, atypical antipsychotics, antidepressants, and a sedative anxiolytic.
Main Results:
- Typical (haloperidol) and atypical (clozapine, risperidone) antipsychotics selectively increased VGLUT2 mRNA in specific thalamic nuclei.
- VGLUT2 protein levels were elevated in the paraventricular thalamus, ventral striatum, and prefrontal cortex following antipsychotic treatment.
- Antidepressants (fluoxetine, desipramine) and diazepam did not affect VGLUT2 expression.
Conclusions:
- Thalamo-limbic glutamatergic pathways are implicated in the mechanism of action of antipsychotics.
- Increased VGLUT2 expression may serve as a biomarker for antipsychotic efficacy.
- Subcortical glutamate neurotransmission presents a potential novel therapeutic target for future antipsychotic drug development.
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