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 postmortem findings in the striatum in schizophrenia.