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.
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.
Burnet
P W
PW
Unit on Neuroendocrine Immunology and Behavior, National Institute of Mental Health, National Institutes of Health, Bethesda, MD 20892.
Michelson
D
D
Smith
M A
MA
Gold
P W
PW
Sternberg
E M
EM
D017371:8-Hydroxy-2-(di-n-propylamino)tetralin / Q000378:metabolism; D000818:Animals; D001345:Autoradiography; D002352:Carrier Proteins / Q000096:biosynthesis*; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism*; D004334:Drug Administration Schedule; D005260:Female; D015870:Gene Expression / Q000187:drug effects; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism*; D007099:Imipramine / Q000494:pharmacology*; D017403:In Situ Hybridization; D008562:Membrane Glycoproteins / Q000096:biosynthesis*; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D009928:Organ Specificity; D017966:Pyramidal Cells / Q000378:metabolism; D012333:RNA, Messenger / Q000032:analysis / Q000378:metabolism*; D011903:Raphe Nuclei / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D011916:Rats, Inbred F344; D011917:Rats, Inbred Lew; D017207:Rats, Sprague-Dawley; D011985:Receptors, Serotonin / Q000096:biosynthesis / Q000378:metabolism*; D012701:Serotonin / Q000378:metabolism; D050486:Serotonin Plasma Membrane Transport Proteins; D013045:Species Specificity; D014316:Tritium
D002352:Carrier Proteins; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins; D012333:RNA, Messenger; D011985:Receptors, Serotonin; D050486:Serotonin Plasma Membrane Transport Proteins; C493232:Slc6a4 protein, rat; D014316:Tritium; D012701:Serotonin; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; D007099:Imipramine