Repeated treatment with haloperidol, but not olanzapine, alters synaptic NMDA receptor composition in rat striatum.
We here show that repeated administration of the first generation antipsychotic haloperidol, but not of the second generation olanzapine, significantly reduced the expression of NMDA subunit NR2A at striatal synapses, whereas both drugs decreased alphaCaMKII protein levels and autophosphorylation degree. Given that alterations in the localization of NMDA receptor regulatory subunits at synapses have been described in experimental parkinsonism, the haloperidol-induced effect on NMDA subunit localization might contribute to drug-induced parkinsonism induced by haloperidol.
Gardoni
Fabrizio
F
Department of Pharmacological Sciences and Centre of Excellence on Neurodegenerative Diseases, University of Milan, via Balzaretti 9, 20133 Milan, Italy.
Frasca
Angelisa
A
Zianni
Elisa
E
Riva
Marco A
MA
Di Luca
Monica
M
Fumagalli
Fabio
F
D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism; D000818:Animals; D014150:Antipsychotic Agents / Q000008:administration & dosage*; D001569:Benzodiazepines / Q000008:administration & dosage*; D054737:Calcium-Calmodulin-Dependent Protein Kinase Kinase / Q000378:metabolism; D003342:Corpus Striatum / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D004334:Drug Administration Schedule; D005786:Gene Expression Regulation / Q000187:drug effects*; D006220:Haloperidol / Q000008:administration & dosage*; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism; D000077152:Olanzapine; D051381:Rats; D017207:Rats, Sprague-Dawley; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism*; D013569:Synapses / Q000187:drug effects* / Q000378:metabolism; D013997:Time Factors
D048868:Adaptor Proteins, Signal Transducing; D014150:Antipsychotic Agents; C501119:Dlg1 protein, rat; D008565:Membrane Proteins; C120997:NR2A NMDA receptor; D016194:Receptors, N-Methyl-D-Aspartate; D001569:Benzodiazepines; D054737:Calcium-Calmodulin-Dependent Protein Kinase Kinase; D006220:Haloperidol; D000077152:Olanzapine