Effects of chronic haloperidol and clozapine treatment on AMPA and kainate receptor binding in rat brain.
BACKGROUND
Alterations in AMPA and kainate receptor binding have been revealed in post-mortem schizophrenic brains. As most patients had been treated with antipsychotics, medication effects cannot be excluded as a possible explanation for these results.


METHODS
Within the framework of this animal study, we investigated [3H]AMPA and [3H]kainate receptor binding in different rat brain regions following 6 months of oral treatment with either haloperidol (1.5 mg/kg/day) or clozapine (45 mg/kg/day).


RESULTS
AMPA receptor binding was increased after haloperidol treatment in the striatum, nucleus accumbens, cingulate cortex, and insular cortex. Clozapine showed increased AMPA receptor binding only in the anterior cingulate cortex. Kainate receptor binding was increased by both drugs in all hippocampal subfields.


CONCLUSIONS
This altered receptor binding may be related to beneficial neuroleptic effects and side effects. Furthermore, neuroleptic therapy may contribute to some of the post-mortem findings in the striatum in schizophrenia.
Schmitt
A
A
Central Institute of Mental Health, Mannheim, Germany. schmitt@zi-mannheim.de
May
B
B
Müller
B
B
Jatzko
A
A
Petroianu
G
G
Braus
D F
DF
Henn
F A
FA
D000818:Animals; D014150:Antipsychotic Agents / Q000494:pharmacology; D001345:Autoradiography; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D003024:Clozapine / Q000494:pharmacology*; D018492:Dopamine Antagonists / Q000494:pharmacology*; D018756:GABA Antagonists / Q000494:pharmacology; D006220:Haloperidol / Q000494:pharmacology*; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D018091:Receptors, AMPA / Q000187:drug effects* / Q000378:metabolism; D018092:Kainic Acid Receptors / Q000187:drug effects* / Q000378:metabolism; D012702:Serotonin Antagonists / Q000494:pharmacology*; D015854:Up-Regulation
D014150:Antipsychotic Agents; D003024:Clozapine; D018492:Dopamine Antagonists; D018756:GABA Antagonists; D006220:Haloperidol; D018091:Receptors, AMPA; D018092:Kainic Acid Receptors; D012702:Serotonin Antagonists