Agonist- and antagonist-induced plasticity of rat 5-HT1A receptor in hippocampal cell culture

✍ Scribed by Mayumi Nishi; Efrain C. Azmitia

• Publisher: John Wiley and Sons
• Year: 1999
• Tongue: English
• Weight: 470 KB
• Volume: 31
• Category: Article
• ISSN: 0887-4476
• DOI: 10.1002/(sici)1098-2396(19990301)31:3<186::aid-syn3>3.0.co;2-o

✦ Synopsis

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 Ϫ8 M) or ipsapirone (IPS) (10 Ϫ9 M) for 10 min blocked the forskolin-stimulated increase in pCREB immunoreactivity. In situ hybridization radioautography revealed that IPS (10 Ϫ9 M) decreased the 5-HT 1A receptor mRNA expression (Ϫ33%) 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 Ϫ7 -10 Ϫ12 M) and IPS (10 Ϫ9 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 (ϩ17% ϳ ϩ39%) 24 h after treatment with the antagonist N-[2-[4-(2-methoxyphenyl)-1-piperazinyl]ethyl]-N-(2-pyridinyl) cyclohexane carboxamide (WAY 100635) (10 Ϫ7 -10 Ϫ12 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.