The effects of antipsychotic drugs on the mRNA levels of serotonin 5HT2A and 5HT2C receptors.
We have looked for both global and regional changes in rat brain mRNA levels encoding serotonin 5HT2A and 5HT2C receptors following acute and chronic administration of antipsychotic drugs. In whole brain clozapine (30 mg/kg/day) elicited a transient rise in 5HT2C mRNA levels after 4 days and chlorpromazine (15 mg/kg/day) elicited a decrease of 20% in 5HT2A mRNA levels after 32 days. Regionally, 32 days treatment with haloperidol (3 mg/kg/day), sulpiride (100 mg/kg/day) or clozapine (10 mg/kg/day) resulted in a drop of approximately 30-40% in 5HT2C mRNA levels in both cortex and cerebellum, and decreases (or non-significant trends) of 15-40% in 5HT2A mRNA levels in hippocampus, brainstem and mid brain. 4 days treatment with clozapine resulted in a 40% rise of 5HT2C mRNA in the mid brain and a 24% rise of 5HT2A mRNA in the nucleus accumbens which were not found after 32 days of treatment. These results demonstrate common chronic effects of typical and atypical drugs but unique short term effects of clozapine.
Buckland
P R
PR
Department of Psychological Medicine, University of Wales College of Medicine, Heath Park, Cardiff, UK. buckland@cardiff.ac.uk
D'Souza
U
U
Maher
N A
NA
McGuffin
P
P
D000818:Animals; D014150:Antipsychotic Agents / Q000494:pharmacology*; D001921:Brain / Q000378:metabolism*; D002746:Chlorpromazine / Q000494:pharmacology; D003024:Clozapine / Q000494:pharmacology; D015536:Down-Regulation; D006220:Haloperidol / Q000494:pharmacology; D008297:Male; D009928:Organ Specificity; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D017208:Rats, Wistar; D044402:Receptor, Serotonin, 5-HT2A; D044405:Receptor, Serotonin, 5-HT2C; D011985:Receptors, Serotonin / Q000096:biosynthesis*; D013469:Sulpiride / Q000494:pharmacology; D013997:Time Factors; D014158:Transcription, Genetic / Q000187:drug effects*; D015854:Up-Regulation
D014150:Antipsychotic Agents; D012333:RNA, Messenger; D044402:Receptor, Serotonin, 5-HT2A; D044405:Receptor, Serotonin, 5-HT2C; D011985:Receptors, Serotonin; D013469:Sulpiride; D003024:Clozapine; D006220:Haloperidol; D002746:Chlorpromazine