Systemic administration of ketamine, a non-competitive antagonist of the N-methyl-d-aspartate receptor (NMDA-R), produces a condition of NMDA-R hypofunction, which is considered one of the putative molecular mechanisms involved in psychosis. In this study, we evaluated the effect of ketamine on glutamatergic markers of the postsynaptic density (PSD), a pivotal site for dopamine-glutamate interaction. We assessed gene expression of Homer1a, α and βCaMKII, and dopamine transporter (DAT) by two different doses of ketamine. These genes were chosen because of their impact on signal transduction and dopamine-glutamate interplay in postsynaptic density. Moreover, Homer1a is modulated by antipsychotics and represents a candidate gene for schizophrenia. Male Sprague-Dawley rats were injected with saline, 12 mg/kg ketamine or 50 mg/kg ketamine, and sacrificed 90 minutes after injections. In situ hybridization histochemistry was used to quantitate the rate of gene expression in rat forebrain. Homer1a was induced by 50 mg/kg ketamine in ventral striatum and by both 50 and 12 mg/kg ketamine in nucleus accumbens, whereas gene expression was not affected in dorsal striatum. αCaMKII was increased by 12 mg/kg ketamine against saline in almost all subregions assessed. βCaMKII was not affected by ketamine. DAT was increased by both doses of ketamine in the ventro-tegmental area and substantia nigra pars compacta. We suggest that these changes may represent molecular adaptations to the perturbation in glutamatergic transmission induced by ketamine blockade of NMDA receptors and may be implicated in molecular alterations occurring in schizophrenia. © 2007 Elsevier Ireland Ltd. All rights reserved.

Ketamine-related expression of glutamatergic postsynaptic density genes: Possible implications in psychosis / Iasevoli, F.; Polese, D.; Ambesi-Impiombato, A.; Muscettola, G.; de Bartolomeis, A.. - In: NEUROSCIENCE LETTERS. - ISSN 0304-3940. - 416:1(2007), pp. 1-5. [10.1016/j.neulet.2007.01.041]

Ketamine-related expression of glutamatergic postsynaptic density genes: Possible implications in psychosis

Polese D.;
2007

Abstract

Systemic administration of ketamine, a non-competitive antagonist of the N-methyl-d-aspartate receptor (NMDA-R), produces a condition of NMDA-R hypofunction, which is considered one of the putative molecular mechanisms involved in psychosis. In this study, we evaluated the effect of ketamine on glutamatergic markers of the postsynaptic density (PSD), a pivotal site for dopamine-glutamate interaction. We assessed gene expression of Homer1a, α and βCaMKII, and dopamine transporter (DAT) by two different doses of ketamine. These genes were chosen because of their impact on signal transduction and dopamine-glutamate interplay in postsynaptic density. Moreover, Homer1a is modulated by antipsychotics and represents a candidate gene for schizophrenia. Male Sprague-Dawley rats were injected with saline, 12 mg/kg ketamine or 50 mg/kg ketamine, and sacrificed 90 minutes after injections. In situ hybridization histochemistry was used to quantitate the rate of gene expression in rat forebrain. Homer1a was induced by 50 mg/kg ketamine in ventral striatum and by both 50 and 12 mg/kg ketamine in nucleus accumbens, whereas gene expression was not affected in dorsal striatum. αCaMKII was increased by 12 mg/kg ketamine against saline in almost all subregions assessed. βCaMKII was not affected by ketamine. DAT was increased by both doses of ketamine in the ventro-tegmental area and substantia nigra pars compacta. We suggest that these changes may represent molecular adaptations to the perturbation in glutamatergic transmission induced by ketamine blockade of NMDA receptors and may be implicated in molecular alterations occurring in schizophrenia. © 2007 Elsevier Ireland Ltd. All rights reserved.
2007
Dopamine; Glutamate; Homer1; Ketamine; PSD; Schizophrenia; Animals; Calcium-Calmodulin-Dependent Protein Kinase Type 2; Calcium-Calmodulin-Dependent Protein Kinases; Carrier Proteins; Cerebral Cortex; Dopamine Plasma Membrane Transport Proteins; Excitatory Amino Acid Antagonists; Gene Expression; Glutamic Acid; Homer Scaffolding Proteins; Ketamine; Male; Nucleus Accumbens; RNA, Messenger; Rats; Rats, Sprague-Dawley; Schizophrenia; Synapses
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Ketamine-related expression of glutamatergic postsynaptic density genes: Possible implications in psychosis / Iasevoli, F.; Polese, D.; Ambesi-Impiombato, A.; Muscettola, G.; de Bartolomeis, A.. - In: NEUROSCIENCE LETTERS. - ISSN 0304-3940. - 416:1(2007), pp. 1-5. [10.1016/j.neulet.2007.01.041]
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11573/1507503
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