Lower cortical serotonin 2A receptors in major depressive disorder, suicide and in rats after administration of imipramine.
We have attempted to replicate studies showing higher levels of serotonin 2A receptors (HTR2A) in the cortex of people with mood disorders and to determine the effects of treating rats with antidepressant drugs on levels of that receptor. In situ [3H]ketanserin binding and autoradiography was used to measure levels of HTR2A in Brodmann's area (BA) 46 and 24 from people with major depressive disorders (MDD, n = 16), bipolar disorders (BD, n = 14) and healthy controls (n = 14) as well as the central nervous system (CNS) of rats (20 per treatment arm) treated for 10 or 28 d with fluoxetine (10 mg/kg/d) or imipramine (20 mg/kg/d). Compared with controls, HTR2A were lower in BA 24, but not BA 46, from people with MDD (p = 0.005); HTR2A were not changed in BD. Levels of HTR2A were lower in BA 24 (p = 0.007), but not BA 46, from people who had died by suicide. Finally, levels of HTR2A were lower in the CNS of rats treated with imipramine, but not fluoxetine, for 28 d, but not 10 d. From our current and previous data we conclude cortical HTR2A are lower in schizophrenia, MDD, people with mood disorders who died by suicide, rats treated with some antipsychotic or some antidepressant drugs. As levels of cortical HTR2A can be affected by the aetiologies of different disorders and mechanisms of action of different drugs, a better understanding of how such changes can occur needs to be elucidated.
The Florey Institute for Neuroscience and Mental Health and the University of Melbourne, Victoria, Australia.
Brian
B
Dean
The Florey Institute for Neuroscience and Mental Health and the University of Melbourne, Victoria, Australia.
Nahed
N
Tawadros
The Florey Institute for Neuroscience and Mental Health and the University of Melbourne, Victoria, Australia.
Myoung Suk
MS
Seo
The Florey Institute for Neuroscience and Mental Health and the University of Melbourne, Victoria, Australia.
Won Je
WJ
Jeon
Department of Psychiatry, University of Melbourne, Victoria, Australia.
Ian
I
Everall
Department of Psychiatry, University of Melbourne, Victoria, Australia.
Elizabeth
E
Scarr
The Florey Institute for Neuroscience and Mental Health and the University of Melbourne, Victoria, Australia.
Andrew
A
Gibbons
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology*; D014150:Antipsychotic Agents / Q000494:pharmacology; D001714:Bipolar Disorder / Q000188:drug therapy / Q000378:metabolism; D002540:Cerebral Cortex / Q000187:drug effects* / Q000378:metabolism; D003865:Major Depressive Disorder / Q000188:drug therapy* / Q000378:metabolism; D005260:Female; D005473:Fluoxetine / Q000494:pharmacology; D005625:Frontal Lobe / Q000187:drug effects / Q000378:metabolism; D006179:Gyrus Cinguli / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D007099:Imipramine / Q000494:pharmacology*; D008297:Male; D008875:Middle Aged; D017207:Rats, Sprague-Dawley; D044402:Receptor, Serotonin, 5-HT2A / Q000378:metabolism*; D013405:Suicide; D055815:Young Adult
D000928:Antidepressive Agents; D014150:Antipsychotic Agents; D044402:Receptor, Serotonin, 5-HT2A; D005473:Fluoxetine; D007099:Imipramine