Effects of chronic 17beta-estradiol treatment on the serotonin 5-HT(1A) receptor mRNA and binding levels in the rat brain.
Acute 17beta-estradiol treatment had been shown to downregulate the 5-HT(1A) receptor mRNA expression in limbic areas of the female rat brain. The aim of the present study was to determine the effects of chronic 17beta-estradiol treatment on 5-HT(1A) receptor mRNA expression and 5-HT(1A) receptor binding in ovariectomized female rats. Using in situ hybridization histochemistry, no alterations were found on the 5-HT(1A) receptor mRNA levels after the estradiol treatment (2 weeks). Radioligand autoradiographic studies using the selective 5-HT(1A) receptor antagonist [(3)H]WAY-100635 revealed reduced receptor binding in the amygdala, hippocampus, perirhinal cortex, and motor cortex after estradiol treatment, whereas no changes were observed in the piriform or retrosplenial cortex. Thus, the previous findings together with the present results indicate that estradiol-induced alterations in 5-HT(1A) receptor mRNA expression appears within hours, but diminishes with chronic treatment when significant changes on the receptor-protein level are apparent. The effects of estradiol treatment on the 5-HT(1A) receptor binding in the limbic areas suggest that estrogen can modulate functions such as learning, memory, cognition, emotional processing, and social behavior. Consequently, estradiol modulation of 5-HT(1A) receptor circuits might be a possible pathway for the estrogen influence in the expression of psychiatric and neurological disorders such as Alzheimer's disease, affective disorders, and schizophrenia.
Osterlund
M K
MK
Department of Clinical Neuroscience, Section of Psychiatry, Karolinska Institute, Karolinska Hospital, S-17176 Stockholm, Sweden.
Halldin
C
C
Hurd
Y L
YL
D000818:Animals; D001923:Brain Chemistry / Q000187:drug effects; D004958:Estradiol / Q000494:pharmacology*; D005260:Female; D015870:Gene Expression / Q000187:drug effects; D010879:Piperazines / Q000494:pharmacology; D011725:Pyridines / Q000494:pharmacology; D012333:RNA, Messenger / Q000032:analysis / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011985:Receptors, Serotonin / Q000235:genetics* / Q000378:metabolism*; D044263:Receptors, Serotonin, 5-HT1; D012702:Serotonin Antagonists / Q000494:pharmacology
D010879:Piperazines; D011725:Pyridines; D012333:RNA, Messenger; D011985:Receptors, Serotonin; D044263:Receptors, Serotonin, 5-HT1; D012702:Serotonin Antagonists; D004958:Estradiol; C090413:N-(2-(4-(2-methoxyphenyl)-1-piperazinyl)ethyl)-N-(2-pyridinyl)cyclohexanecarboxamide