[Effect of antipsychotics on glutaminergic neural transmission in the animal model].
Post-mortem investigations have confirmed that glutamatergic NMDA, AMPA, and kainate receptors are involved in the pathophysiology of schizophrenia. It is still unclear, however, whether the altered number of receptors is caused by the disease itself or the medication. Therefore, animal models were investigated for effects of antipsychotic medication after treatment periods of up to 6 months, the results of which are summarized here. Generally, NMDA receptor binding was found to be increased in striatum and nucleus accumbens after therapy with haloperidol, whereas clozapine only increased the number of receptors in nucleus accumbens. While haloperidol led to an increase in AMPA receptors in the posterior cingulate gyrus, striatum, insular cortex, and n. accumbens, clozapine was found to elevate ligand binding in the anterior cingulate gyrus and infralimbic cortex. Although kainate receptor binding was increased in hippocampus by both antipsychotics, clozapine was significantly more effective. In conclusion, data reveal different effects from the typical neuroleptic haloperidol and the atypical antipsychotic clozapine. The results suggest that post-mortem findings in patients with schizophrenia may at least partially be explained by drug effects and plasticity changes induced by long-term medication with antipsychotics.
Schmitt
A
A
Zentralinstitut für Seelische Gesundheit, Universität Mannheim, Germany.
May
B
B
Müller
B
B
Zink
M
M
Braus
D F
DF
Henn
F A
FA
D000818:Animals; D014150:Antipsychotic Agents / Q000494:pharmacology*; D001921:Brain / Q000187:drug effects* / Q000473:pathology; D003024:Clozapine / Q000494:pharmacology; D004195:Disease Models, Animal; D006220:Haloperidol / Q000494:pharmacology; D006801:Humans; D008134:Long-Term Care; D009473:Neuronal Plasticity / Q000187:drug effects; D009474:Neurons / Q000187:drug effects / Q000473:pathology; D051381:Rats; D017470:Receptors, Glutamate / Q000187:drug effects*; D012559:Schizophrenia / Q000188:drug therapy* / Q000473:pathology; D009435:Synaptic Transmission / Q000187:drug effects*
D014150:Antipsychotic Agents; D017470:Receptors, Glutamate; D003024:Clozapine; D006220:Haloperidol