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

Brain Res. 1994 Feb 28;638(1-2):311-24. doi: 10.1016/0006-8993(94)90664-5.

Abstract

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.

Publication types

  • Comparative Study

MeSH terms

  • 8-Hydroxy-2-(di-n-propylamino)tetralin / metabolism
  • Animals
  • Autoradiography
  • Carrier Proteins / biosynthesis*
  • Cerebral Cortex / drug effects
  • Cerebral Cortex / metabolism*
  • Drug Administration Schedule
  • Female
  • Gene Expression / drug effects
  • Hippocampus / drug effects
  • Hippocampus / metabolism*
  • Imipramine / pharmacology*
  • In Situ Hybridization
  • Membrane Glycoproteins / biosynthesis*
  • Membrane Transport Proteins*
  • Nerve Tissue Proteins*
  • Neurons / drug effects
  • Neurons / metabolism
  • Organ Specificity
  • Pyramidal Cells / metabolism
  • RNA, Messenger / analysis
  • RNA, Messenger / metabolism*
  • Raphe Nuclei / drug effects
  • Raphe Nuclei / metabolism*
  • Rats
  • Rats, Inbred F344
  • Rats, Inbred Lew
  • Rats, Sprague-Dawley
  • Receptors, Serotonin / biosynthesis
  • Receptors, Serotonin / metabolism*
  • Serotonin / metabolism
  • Serotonin Plasma Membrane Transport Proteins
  • Species Specificity
  • Tritium

Substances

  • Carrier Proteins
  • Membrane Glycoproteins
  • Membrane Transport Proteins
  • Nerve Tissue Proteins
  • RNA, Messenger
  • Receptors, Serotonin
  • Serotonin Plasma Membrane Transport Proteins
  • Slc6a4 protein, rat
  • Tritium
  • Serotonin
  • 8-Hydroxy-2-(di-n-propylamino)tetralin
  • Imipramine