Increase in levels and ex vivo release of thyrotrophin-releasing hormone (TRH) in specific regions of the CNS of the rat by chronic treatment with antidepressants.
This study has investigated the effects of chronic treatment with amitriptyline, chlorimipramine, mianserin and metergoline on levels and ex vivo release of thyrotrophin-releasing hormone (TRH), 5-hydroxytryptamine (5-HT) and 5-hydroxyindoleacetic acid (5-HIAA) in specific regions of the brain and lumbar spinal cord of the rat. All four treatments caused a significant increase in levels of TRH in the lumbar spinal cord with amitriptyline producing the most marked effect. Amitriptyline alone caused a similar marked increase in levels of TRH in the nucleus accumbens and suprachiasmatic nucleus but none of the treatments had a significant effect on the TRH content of the median eminence or septal nuclei. Potassium-induced release of TRH and 5-HT ex vivo was measured from tissue slices of the nucleus accumbens, septal nuclei and lumbar spinal cord after treatment with amitriptyline and mianserin. An increase in release of TRH was observed only from tissue slices of areas where increased levels of the peptide had occurred; namely nucleus accumbens and lumbar spinal cord after administration of amitriptyline and lumbar spinal cord after mianserin. None of the drugs significantly altered the ex vivo release of 5-HT or 5-HIAA. The results are discussed in relation to a possible interaction between TRH and 5-HT receptors in the antidepressant action of these drugs.
Lighton
C
C
Bennett
G W
GW
Marsden
C A
CA
D000639:Amitriptyline / Q000494:pharmacology; D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology*; D002490:Central Nervous System / Q000187:drug effects*; D002997:Clomipramine / Q000494:pharmacology; D006897:Hydroxyindoleacetic Acid / Q000378:metabolism*; D066298:In Vitro Techniques; D008297:Male; D008711:Metergoline / Q000494:pharmacology; D008803:Mianserin / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D012701:Serotonin / Q000378:metabolism*; D013973:Thyrotropin-Releasing Hormone / Q000378:metabolism*
D000928:Antidepressive Agents; D008711:Metergoline; D000639:Amitriptyline; D008803:Mianserin; D012701:Serotonin; D006897:Hydroxyindoleacetic Acid; D013973:Thyrotropin-Releasing Hormone; D002997:Clomipramine