The effect of chronic imipramine administration on the densities of 5-HT1A and 5-HT2 receptors and the abundances of 5-HT receptor and transporter mRNA in the cortex, hippocampus and dorsal raphe of three strains of rat.
Burnet PW., Michelson D., Smith MA., Gold PW., Sternberg EM.
We have recently demonstrated that the LEW/N rat contains lower concentrations of cortical and hippocampal 5-HT1A receptors compared with the F344/N and out-bred HSD rats. To further characterize these strains, we investigated the effect of chronic (8 wk) imipramine administration (5 mg/kg/day) on 5-HT1A and 5-HT2 receptor densities and mRNA in the cortex and hippocampus and 5-HT transporter mRNA in the dorsal raphe of LEW/N, HSD, and F344/N rats, using quantitative autoradiography and in situ hybridization histochemistry. After imipramine treatment, a significant increase in the levels of hippocampal 5-HT1A receptors, but not mRNA, was observed in LEW/N rats while the abundance of hippocampal 5-HT1A receptor mRNA, but not 5-HT1A receptor densities, decreased in F344/N rats. Cortical and hippocampal 5-HT2 receptor densities, but not mRNA, significantly decreased after imipramine administration in all three strains. Finally, 5-HT1A receptor densities and the abundance of mRNAs encoding the 5-HT1A receptor and 5-HT transporter in the dorsal raphe remained unaltered after imipramine administration in all three strains. The effects of imipramine on the levels of cortical and hippocampal 5-HT1A and 5-HT2 receptors and their transcripts, therefore, appear to be strain-dependent. The implications of these findings are discussed.