Antipsychotic-induced alterations in D2 dopamine receptor interacting proteins within the cortex.
Current antipsychotic treatment involves the regulation of D2 dopamine receptor activity in the brain. Here, we examined the effects of chronic haloperidol and clozapine on cortical D2 dopamine receptors and six different dopamine receptor interacting proteins. Using comparative immunoblot analysis, we found that treatment with either haloperidol or clozapine increased D2 dopamine receptors, calcium activator protein for secretion, protein 4.1N, and neuronal calcium sensor-1 expression. Treatment with clozapine increased calmodulin and spinophilin expression, while treatment with haloperidol decreased expression of these two dopamine receptor interacting proteins. Neither antipsychotic drug was found to have an effect on filamin-A expression. These findings underscore a role for cortical D2 dopamine receptor in the mechanism of antipsychotic drug action, and suggest dopamine receptor interacting proteins as novel targets in antipsychotic drug development.
Kabbani
Nadine
N
Department of Neurobiology, Yale University School of Medicine, New Haven, Connecticut, USA. nkabbani@pasteur.fr
Levenson
Robert
R
D000818:Animals; D014150:Antipsychotic Agents / Q000494:pharmacology*; D015153:Blotting, Western / Q000379:methods; D002135:Calcium-Binding Proteins / Q000378:metabolism*; D002540:Cerebral Cortex / Q000187:drug effects*; D003024:Clozapine / Q000494:pharmacology*; D003598:Cytoskeletal Proteins / Q000378:metabolism*; D015870:Gene Expression / Q000187:drug effects; D006220:Haloperidol / Q000494:pharmacology*; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D051580:Neuronal Calcium-Sensor Proteins; D009479:Neuropeptides / Q000378:metabolism*; D017448:Receptors, Dopamine D2 / Q000378:metabolism
D014150:Antipsychotic Agents; D002135:Calcium-Binding Proteins; D003598:Cytoskeletal Proteins; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; D051580:Neuronal Calcium-Sensor Proteins; D009479:Neuropeptides; D017448:Receptors, Dopamine D2; C120557:erythrocyte membrane protein band 4.1-like 1; C101464:frequenin calcium sensor proteins; D003024:Clozapine; D006220:Haloperidol