Antipsychotics increase vesicular glutamate transporter 2 (VGLUT2) expression in thalamolimbic pathways

Moutsimilli L(1), Farley S, El Khoury MA, Chamot C, Sibarita JB, Racine V, El
Mestikawy S, Mathieu F, Dumas S, Giros B, Tzavara ET.

Author information:
(1)INSERM U513, 8 rue du General Sarrail, Créteil 94010, France.

Recently the two vesicular-glutamate-transporters VGLUT1 and VGLUT2 have been
cloned and characterized. VGLUT1 and VGLUT2 together label all glutamatergic
neurons, but because of their distinct expression patterns in the brain they
facilitate our ability to define between a VGLUT1-positive cortical and a
VGLUT2-positive subcortical glutamatergic systems. We have previously
demonstrated an increased cortical VGLUT1 expression as marker of antidepressant
activity. Here, we assessed the effects of different psychotropic drugs on brain
VGLUT2 mRNA and protein expression. The typical antipsychotic haloperidol, and
the atypicals clozapine and risperidone increased VGLUT2 mRNA selectively in the
central medial/medial parafascicular, paraventricular and intermediodorsal
thalamic nuclei; VGLUT2 protein was accordingly amplified in paraventricular and
ventral striatum and in prefrontal cortex. The antidepressants fluoxetine and
desipramine and the sedative anxiolytic diazepam had no effect. These results
highlight the implication of thalamo-limbic glutamatergic pathways in the action
of antipsychotics. Increased VGLUT2 expression in these neurons might constitute
a marker for antipsychotic activity and subcortical glutamate neurotransmission
might be a possible novel target for future generation antipsychotics.

DOI: 10.1016/j.neuropharm.2007.10.022
PMID: 18155072 [Indexed for MEDLINE]

Auteurs Bordeaux Neurocampus