Brain region-specific alterations of 5-HT2A and 5-HT2C receptors in serotonin transporter knockout mice.
The aim of the present studies was to determine the effects of reduced or absent serotonin (5-HT) transporters (5-HTTs) on 5-HT2A and 5-HT2C receptors. The density of 5-HT2C receptors was significantly increased in the amygdala and choroid plexus of 5-HTT knockout mice. On the other hand, the density of 5-HT2A receptors was significantly increased in the hypothalamus and septum, but reduced in the striatum, of 5-HTT knockout mice. However, 5-HT2A mRNA was not changed in any brain region measured. 5-HT2C mRNA was significantly reduced in the choroid plexus and lateral habenula nucleus of these mice. The function of 5-HT2A receptors was evaluated by hormonal responses to (+/-)-1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI). Oxytocin, but not adrenocorticotrophic hormone or corticosterone, responses to DOI were significantly greater in 5-HTT knockout mice. In addition, Gq and G11 proteins were not significantly changed in any brain region measured. The present results suggest that the constitutive alteration in the function of 5-HTTs changes the density of 5-HT2A and 5-HT2C receptors in a brain region-specific manner. These changes may not be mediated by alterations in their gene expression or in the level of Gq/11 proteins. The alterations in these receptors may be related to the altered behaviors of 5-HTT knockout mice.
Li
Qian
Q
Laboratory of Clinical Science, National Institute of Mental Health, National Institutes of Health, Bethesda, Maryland 20892-1264, USA. qianli@codon.nih.gov
Wichems
Christine H
CH
Ma
Li
L
Van de Kar
Louis D
LD
Garcia
Francisca
F
Murphy
Dennis L
DL
D000818:Animals; D001007:Anxiety / Q000235:genetics / Q000473:pathology; D001345:Autoradiography; D001921:Brain / Q000378:metabolism* / Q000473:pathology; D002352:Carrier Proteins / Q000235:genetics; D005260:Female; D043802:GTP-Binding Protein alpha Subunits, Gq-G11; D020962:Heterotrimeric GTP-Binding Proteins / Q000378:metabolism; D006579:Heterozygote; D006720:Homozygote; D017403:In Situ Hybridization; D007215:Indophenol / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D008297:Male; D008562:Membrane Glycoproteins / Q000172:deficiency* / Q000235:genetics; D026901:Membrane Transport Proteins; D051379:Mice; D018345:Mice, Knockout; D008818:Mice, Neurologic Mutants; D009419:Nerve Tissue Proteins; D009928:Organ Specificity; D012333:RNA, Messenger / Q000378:metabolism; D044402:Receptor, Serotonin, 5-HT2A; D044405:Receptor, Serotonin, 5-HT2C; D011985:Receptors, Serotonin / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D012702:Serotonin Antagonists / Q000494:pharmacology; D050486:Serotonin Plasma Membrane Transport Proteins; D017366:Serotonin Receptor Agonists / Q000493:pharmacokinetics
D002352:Carrier Proteins; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins; D012333:RNA, Messenger; D044402:Receptor, Serotonin, 5-HT2A; D044405:Receptor, Serotonin, 5-HT2C; D011985:Receptors, Serotonin; D012702:Serotonin Antagonists; D050486:Serotonin Plasma Membrane Transport Proteins; D017366:Serotonin Receptor Agonists; C493231:Slc6a4 protein, mouse; C113896:dimethoxy-4-indophenyl-2-aminopropane; D007215:Indophenol; D043802:GTP-Binding Protein alpha Subunits, Gq-G11; D020962:Heterotrimeric GTP-Binding Proteins