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Agonist‐ and antagonist‐induced plasticity of rat 5‐HT 1A receptor in hippocampal cell culture
Author(s) -
Nishi Mayumi,
Azmitia Efrain C.
Publication year - 1999
Publication title -
synapse
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.809
H-Index - 106
eISSN - 1098-2396
pISSN - 0887-4476
DOI - 10.1002/(sici)1098-2396(19990301)31:3<186::aid-syn3>3.0.co;2-o
Subject(s) - 5 ht1a receptor , ipsapirone , medicine , agonist , endocrinology , receptor , 8 oh dpat , receptor antagonist , biology , receptor expression , hippocampal formation , chemistry , 5 ht receptor , antagonist , serotonin , buspirone
We examined the response and regulation of 5‐HT 1A receptor on hippocampal cultured fetal neurons grown in the absence of serotonin and steroids using three experimental designs: 1) functional response using an antibody against phosphorylated cyclic adenosine monophosphate response element binding protein (pCREB); 2) transcriptional regulation using in situ hybridization; and 3) translational expression using antipeptide 5‐HT 1A receptor antibody. Pretreatment of cultured hippocampal cells with the agonist 8‐hydroxy‐2‐(di‐N‐propylamino)‐tetralin (8‐OH‐DPAT) (10 −8 M) or ipsapirone (IPS) (10 −9 M) for 10 min blocked the forskolin‐stimulated increase in pCREB immunoreactivity. In situ hybridization radioautography revealed that IPS (10 −9 M) decreased the 5‐HT 1A receptor mRNA expression (−33%) after a 24‐h treatment. The decrease in 5‐HT 1A receptor mRNA was accompanied by a change in protein immunoreactivity using a 5‐HT 1A receptor antipeptide antibody. Computer‐assisted morphometric analyses showed a reduction in the 5‐HT 1A receptor immunoreactive (IR) intensity as compared to control 24 h after treatment with 8‐OH‐DPAT (10 −7 –10 −12 M) and IPS (10 −9 M). Thus, fetal hippocampal neurons have a functional 5‐HT 1A receptor that is downregulated at both the transcription and translation levels. In addition, we found increased 5‐HT 1A receptor‐IR intensity (+17% ∼ +39%) 24 h after treatment with the antagonist N‐[2‐[4‐(2‐methoxyphenyl)‐1‐piperazinyl]ethyl]‐N‐(2‐pyridinyl) cyclohexane carboxamide (WAY 100635) (10 −7 –10 −12 M). Our results indicate that the 5‐HT 1A receptor is sensitive to both agonists (downregulation) and antagonists (upregulation) in hippocampal fetal neurons grown in the absence of serotonin and steroids. Synapse 31:186–195, 1999. © 1999 Wiley‐Liss, Inc.