Proteome analysis after co-administration of clozapine or haloperidol to MK-801-treated rats.
MK-801, a glutamergic, N-methyl-D-aspartate (NMDA)-receptor antagonist that mediates neurotransmission and has psychotomimetic properties, giving schizophrenia-like symptom. The objective of this study was to investigate the effects on the thalamic and cortical proteome of one typical (haloperidol) and one atypical (clozapine) antipsychotic drug in interaction with MK-801 in rats. Rats received subcutaneous injections of MK-801 or vehicle (controls) or MK-801 together with concurrent administration of haloperdol or clozapine for eight days. Protein samples from thalamus and cortex were analyzed with two-dimensional gel electrophoresis in combination with mass spectrometry. MK-801 induced alterations in the levels of three proteins in both cortex and thalamus. Clozapine reversed all the protein changes. Haloperidol reversed two. Both antipsychotics induced new protein changes in both cortex and thalamus not seen after MK-801-treatment by alone. In conclusion, the MK-801 animal model shows potential for investigation of different antipsychotic drugs and biochemical treatment effects in schizophrenia.
Paulson
L
L
Institute of Neuroscience and Physiology, Göteborg University, Mölndal, Sweden. linda.paulson@neuro.gu.se
Martin
P
P
Ljung
E
E
Blennow
K
K
Davidsson
P
P
D000818:Animals; D014150:Antipsychotic Agents / Q000008:administration & dosage; D003024:Clozapine / Q000008:administration & dosage*; D004195:Disease Models, Animal; D016291:Dizocilpine Maleate / Q000008:administration & dosage*; D004338:Drug Combinations; D018691:Excitatory Amino Acid Antagonists / Q000008:administration & dosage; D006220:Haloperidol / Q000008:administration & dosage*; D008297:Male; D020543:Proteome / Q000032:analysis* / Q000096:biosynthesis / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D012559:Schizophrenia / Q000378:metabolism; D012702:Serotonin Antagonists / Q000008:administration & dosage; D013788:Thalamus / Q000187:drug effects / Q000378:metabolism
D014150:Antipsychotic Agents; D004338:Drug Combinations; D018691:Excitatory Amino Acid Antagonists; D020543:Proteome; D012702:Serotonin Antagonists; D016291:Dizocilpine Maleate; D003024:Clozapine; D006220:Haloperidol