Cortisol-mediated downregulation of the serotonin 1A receptor subtype in the Gulf toadfish, Opsanus beta.
In both mammals and teleost fish, serotonin stimulates cortisol secretion via the 5-HT1A receptor. Additionally, a negative feedback loop exists in mammals whereby increased circulating levels of cortisol inhibit 5-HT1A receptor activity. To investigate the possibility of such a feedback mechanism in teleosts, plasma cortisol levels and signaling in Gulf toadfish (Opsanus beta) were manipulated and the role of cortisol in the control of 5-HT1A evaluated. Despite a significant 4-fold increase in plasma [cortisol], crowded toadfish expressed similar amounts of 5-HT1A mRNA transcript as uncrowded toadfish; whereas, cortisol-implanted fish possessed 41.8% less 5-HT1A mRNA transcript compared to vehicle-implanted controls. This cortisol effect appeared to be reversed in RU486-injected fish, which blocks glucocorticoid receptors, as these fish expressed nearly twice as much 5-HT1A receptor transcript as the vehicle-injected fish despite significantly elevated cortisol levels. The binding affinity for the 5-HT1A receptor in the brain did not vary between any groups; however, maximum binding was significantly higher in uncrowded toadfish compared to crowded, and the same significant difference was observed between the maximum binding of vehicle and cortisol-implanted fish. The opposite trend was seen in RU486-injected and vehicle-injected fish, with RU486-injected fish having significantly higher maximal binding compared to vehicle-injected controls. Injection with the 5-HT1A receptor agonist 8-hydroxy-2-(di-n-propylamino)tetralin revealed an inhibition of cortisol secretion that was independent of 5-HT1A transcript and protein binding. These results suggest that cortisol plays a role in regulating the 5-HT1A receptor via GR-mediated pathways; however, further study is necessary to elucidate how and where this inhibition is mediated.
Rosenstiel School of Marine and Atmospheric Science, University of Miami, Miami, FL 33149-1098, USA. lmedeiros@uidaho.edu
Lea R
LR
Medeiros
M Danielle
MD
McDonald
D017371:8-Hydroxy-2-(di-n-propylamino)tetralin / Q000494:pharmacology; D000818:Animals; D024541:Batrachoidiformes / Q000235:genetics* / Q000378:metabolism*; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D015536:Down-Regulation / Q000187:drug effects; D025461:Feedback, Physiological / Q000187:drug effects; D006854:Hydrocortisone / Q000097:blood / Q000235:genetics* / Q000378:metabolism*; D015735:Mifepristone / Q000494:pharmacology; D011485:Protein Binding / Q000187:drug effects; D044282:Receptor, Serotonin, 5-HT1A / Q000235:genetics* / Q000378:metabolism*; D011965:Receptors, Glucocorticoid / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D012701:Serotonin / Q000235:genetics / Q000378:metabolism; D058825:Serotonin 5-HT1 Receptor Agonists / Q000494:pharmacology
D011965:Receptors, Glucocorticoid; D058825:Serotonin 5-HT1 Receptor Agonists; D044282:Receptor, Serotonin, 5-HT1A; D015735:Mifepristone; D012701:Serotonin; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; D006854:Hydrocortisone