Long-term effects of olanzapine, risperidone, and quetiapine on serotonin 1A, 2A and 2C receptors in rat forebrain regions.
BACKGROUND
Serotonin (5-HT) and its receptors have been implicated in various neuropsychiatric disorders. Altered serotonergic neurotransmission and interactions between 5-HT and dopamine (DA) systems may contribute to the pathophysiology of idiopathic psychotic or manic disorders. Interactions with 5-HT receptors may also contribute to special properties of modern antipsychotic drugs not yet evaluated for long-term effects on 5-HT receptors.


OBJECTIVE
We surveyed effects of newer atypical antipsychotics on 5-HT receptor types 1A, 2A, and 2C in rat forebrain regions by quantitative receptor autoradiography with selective radioligands following 28 days of continuous infusion of drugs or control vehicle.


RESULTS
Infusion of olanzapine, risperidone, and quetiapine increased 1A, but decreased 2A receptor labeling in frontal cerebral cortex. Olanzapine decreased binding at 2C receptors in hippocampal CA(1) and CA(3) regions and perhaps entorhinal cortex; olanzapine, but neither risperidone nor quetiapine, also decreased 2C labeling in caudate-putamen.


CONCLUSIONS
The findings suggest that altered 5-HT(1A) and 5-HT(2A)receptor levels in frontal cortex, and 5-HT(2C) receptors in other forebrain regions, may contribute to psychopharmacological properties of these novel atypical antipsychotic agents, perhaps including their antipsychotic or antimanic actions, and low risk of adverse extrapyramidal effects.
Tarazi
Frank I
FI
Consolidated Department of Psychiatry and Neuroscience Program, Harvard Medical School, Boston, MA 02115, USA. ftarazi@hms.harvard.edu
Zhang
Kehong
K
Baldessarini
Ross J
RJ
D000818:Animals; D014150:Antipsychotic Agents / Q000494:pharmacology; D001569:Benzodiazepines; D001667:Binding, Competitive / Q000187:drug effects; D002525:Cerebellar Cortex / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D003987:Dibenzothiazepines / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D018728:Entorhinal Cortex / Q000187:drug effects / Q000378:metabolism; D006624:Hippocampus / Q000166:cytology / Q000187:drug effects; D007260:Infusion Pumps; D008297:Male; D009714:Nucleus Accumbens / Q000187:drug effects / Q000378:metabolism; D000077152:Olanzapine; D010890:Pirenzepine / Q000031:analogs & derivatives* / Q000494:pharmacology*; D016548:Prosencephalon / Q000187:drug effects* / Q000378:metabolism; D011699:Putamen / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D000069348:Quetiapine Fumarate; D011869:Radioligand Assay; D051381:Rats; D017207:Rats, Sprague-Dawley; D044402:Receptor, Serotonin, 5-HT2A; D044405:Receptor, Serotonin, 5-HT2C; D011985:Receptors, Serotonin / Q000187:drug effects* / Q000378:metabolism; D044263:Receptors, Serotonin, 5-HT1; D018967:Risperidone / Q000494:pharmacology*; D012702:Serotonin Antagonists / Q000494:pharmacology; D017367:Selective Serotonin Reuptake Inhibitors / Q000494:pharmacology; D013997:Time Factors
D014150:Antipsychotic Agents; D001569:Benzodiazepines; D003987:Dibenzothiazepines; D000077152:Olanzapine; D010890:Pirenzepine; D000069348:Quetiapine Fumarate; D044402:Receptor, Serotonin, 5-HT2A; D044405:Receptor, Serotonin, 5-HT2C; D011985:Receptors, Serotonin; D044263:Receptors, Serotonin, 5-HT1; D018967:Risperidone; D012702:Serotonin Antagonists; D017367:Selective Serotonin Reuptake Inhibitors