Regulation of beta 1-adrenergic receptor mRNA and ligand binding by antidepressant treatments and norepinephrine depletion in rat frontal cortex.
The number of beta 1-adrenergic receptor (beta 1AR) binding sites is decreased by chronic antidepressant treatments, including electroconvulsive seizure (ECS) and imipramine, whereas administration of agents that deplete norepinephrine (NE) increases the number of beta 1AR binding sites in cerebral cortex. The present study was carried out to examine the influence of these treatments on levels of beta 1AR mRNA in frontal cortex to study the molecular mechanisms that underlie the regulation of beta 1ARs in brain. Levels of beta 1AR mRNA were measured by RNase protection analysis using a riboprobe derived from rat beta 1AR cDNA, and the levels of beta AR binding were measured using the nonselective ligand [3H]CGP-12177. Studies to verify the specificity of the RNase protection assay revealed that the distribution of beta 1AR mRNA was in agreement with the reported distribution of beta 1AR ligand binding: Levels of beta 1AR mRNA were highest in cerebral cortex or frontal cortex, intermediate in neostriatum, hippocampus, lung, and heart, and lowest in cerebellum, kidney, and liver. Chronic ECS treatment (once daily for 10 days) significantly decreased levels of beta AR ligand binding and resulted in a corresponding, time-dependent down-regulation of beta 1AR mRNA levels in frontal cortex. However, imipramine administration regulated levels of beta 1AR mRNA in a biphasic manner, with treatments for 7-14 days increasing and treatments for 18-21 days decreasing levels of beta 1AR mRNA in frontal cortex. In contrast, levels of [3H]CGP-12177 ligand binding were decreased at all time points examined (3-21 days).(ABSTRACT TRUNCATED AT 250 WORDS)
Department of Psychiatry, Yale University School of Medicine, New Haven, Connecticut 06508.
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D000818:Animals; D004597:Electroshock; D005625:Frontal Lobe / Q000187:drug effects / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000187:drug effects*; D007099:Imipramine / Q000494:pharmacology*; D008297:Male; D009693:Nucleic Acid Hybridization; D016627:Oxidopamine / Q000494:pharmacology; D011412:Propanolamines / Q000378:metabolism; D015347:RNA Probes; D012333:RNA, Messenger / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011943:Receptors, Adrenergic, beta / Q000235:genetics* / Q000378:metabolism; D012260:Ribonucleases
D011412:Propanolamines; D015347:RNA Probes; D012333:RNA, Messenger; D011943:Receptors, Adrenergic, beta; D016627:Oxidopamine; D012260:Ribonucleases; D007099:Imipramine; C033394:CGP 12177