Central 5-hydroxytryptamine-2A receptor expression in transgenic mice bearing a glucocorticoid receptor antisense.
Transgenic mice bearing a transgene coding for a glucocorticoid receptor antisense mRNA that partially blocks glucocorticoid receptor expression were used to investigate the long-term effect of hypothalamic-pituitary-adrenal dysfunction on brain 5-hydroxytryptamine-2A (5-HT2A) receptor expression. The brain 5-HT2A receptor mRNA levels in transgenic mice were measured by in situ hybridization and compared to those in control mice. We also studied the effect of a 3-week treatment with fluoxetine on brain 5-HT2A receptor expression in the transgenic mice. No difference in 5-HT2A mRNA levels was observed between transgenic and control mice in cortical or striatal regions, and fluoxetine treatment was without effect. No difference in hypothalamic 5-HT2A mRNA levels was observed between transgenic and control mice, while fluoxetine treatment increased these levels in both transgenic as well as in the hypothalamic ventromedial and paraventricular nuclei of control mice. 5-HT2A receptor mRNA levels were similar in hippocampal CA1 and CA2 subregions of control and transgenic, but were lower in the CA3 and CA4 subregions of transgenic mice. Fluoxetine had no effect on 5-HT2A mRNA levels of transgenic mice but reduced control mouse 5-HT2A receptor mRNA levels in the CA3 subregion. These results suggest that impaired glucocorticoid receptor function can affect hippocampal 5-HT2A receptor expression in transgenic mice and that this is not corrected by fluoxetine treatment.
Cyr
M
M
Oncology and Molecular Endocrinology Research Center, CHUQ, Pavillon CHUL, Laval University, Sainte-Foy, Quebec, Canada.
Charbonneau
C
C
Morissette
M
M
Rochford
J
J
Barden
N
N
Di Paolo
T
T
D000818:Animals; D002540:Cerebral Cortex / Q000378:metabolism; D016373:DNA, Antisense; D003863:Depression / Q000378:metabolism; D005260:Female; D005473:Fluoxetine / Q000494:pharmacology; D015870:Gene Expression / Q000187:drug effects / Q000502:physiology; D006624:Hippocampus / Q000378:metabolism; D017403:In Situ Hybridization; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009924:Organ Culture Techniques; D012333:RNA, Messenger / Q000032:analysis; D044402:Receptor, Serotonin, 5-HT2A; D011965:Receptors, Glucocorticoid / Q000235:genetics*; D011985:Receptors, Serotonin / Q000235:genetics* / Q000378:metabolism; D012701:Serotonin / Q000378:metabolism*; D017367:Selective Serotonin Reuptake Inhibitors / Q000494:pharmacology; D013045:Species Specificity
D016373:DNA, Antisense; D005473:Fluoxetine; D012333:RNA, Messenger; D044402:Receptor, Serotonin, 5-HT2A; D011965:Receptors, Glucocorticoid; D011985:Receptors, Serotonin; D012701:Serotonin; D017367:Selective Serotonin Reuptake Inhibitors