Effect of chronic imipramine treatment on beta-1 adrenergic receptor mRNA and ligand binding

The present study was carried out to examine the influence of imipramine treatment on levels of beta-1 adrenergic receptor (AR) mRNA in various brain regions to study the molecular mechanisms that underlie the regulation of beta-1 AR in rat brain. Levels of beta-1 AR mRNA were measured by RNase protection analysis using a riboprobe derived from rat beta-1 AR cDNA, and the levels of beta-1 AR binding were measured using the ligand H-3-dihydroalprenolol studies to verify the specificity of the RNase protection assay revealed that the distribution of beta-1 AR mRNA was in agreement with the reported distribution of beta-1 AR ligand binding. Levels of beta-1 mRNA were highest in cerebral cortex, intermediate in hippocampus and neostriatum, and lowest in cerebellum. Imipramine administration regulated levels of beta-1 AR mRNA in a biphasic manner in cerebral cortex and hippocampus, with treatments for 14 days increasing and treatments for 21 days decreasing levels of beta-1 AR mRNA. In contrast, levels of H-3-dihydroalprenolol ligand binding were decreased at both time points examined. In brainstem and midbrain, however, no change was observed neither in levels of beta-1 AR mRNA nor in levels of H-3-dihydroalprenolol ligand binding. The results demonstrate that beta-1 AR mRNA and ligand binding in cortex and hippocampus are regulated in a complex manner by imipramine, not predicted by changes in ligand binding.