2251 – Cortical and subcortical gene-expression imaging by different n-methyl-daspartate receptor (nmda-r) antagonists at glutammatergic synapses: implications for dopamine-glutamate interplay in psychoses - 09/07/13
Résumé |
Introduction |
According to the NMDA-R hypofunction hypothesis of psychosis, the administration of certain antagonists at NMDA-R, such as ketamine, may exacerbate psychotic symptoms in humans and provide a preclinical model of psychosis. Both ketamine and antipsychotic drugs induce molecular changes in genes of the post-synaptic density (PSD), involved in glutamate signaling and dopamine-glutamate interplay.
Memantine, an antagonist/partial agonist at NMDA-Rs with procognitive properties, has been proposed as an adjunctive treatment for schizophrenia.
Aims |
We tested the hypothesis that memantine and propsychotic NMDA-Rs antagonists (ketamine and MK-801) may elicit divergent molecular changes at glutamatergic synapses.
Methods |
Sprague-Dawley rats were treated by:
1) | vehicle; |
2) | MK-801 0.8mg/kg; |
3) | memantine 5mg/kg; |
4) | ketamine 25mg/kg; |
5) | ketamine 50mg/kg. |
We compared, by in situ hybridization histochemistry, the expression of PSD genes in cortical and striatal brain regions.
Results |
Homer1a expression was significantly induced by ketamine 25mg/kg and reduced by MK-801 in striatum and cortex. Arc expression was significantly induced by ketamine and memantine in the cortex and by MK-801 in nucleus accumbens. Homer1b/c expression was significantly decreased by ketamine compared to vehicle in motor cortex and dorsolateral striatum. PSD-95 expression was significantly decreased by MK-801 compared to vehicle in all striatal regions and by ketamine in dorsomedial striatum.
Conclusions |
These results demonstrate that NMDA-Rs antagonists with different pharmacological properties trigger different molecular changes at glutamatergic synapses. These results are consistent with the different clinical profiles of these compounds and with the observation that NMDA-R blockade is not necessarily associated to psychosis exacerbation.
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Vol 28 - N° S1
P. 1 - 2013 Retour au numéro
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- 2250 – Aging and the neural correlates of emotional prosody discrimintation
- L.R. Demenescu, K. Mathiak
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- H. Al-Modallal
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