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-HT_1A receptor. Additionally, a negative feedback loop exists in mammals whereby increased circulating levels of cortisol inhibit 5-HT_1A 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-HT_1A evaluated. Despite a significant 4-fold increase in plasma [cortisol], crowded toadfish expressed similar amounts of 5-HT_1A mRNA transcript as uncrowded toadfish; whereas, cortisol-implanted fish possessed 41.8% less 5-HT_1A 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-HT_1A receptor transcript as the vehicle-injected fish despite significantly elevated cortisol levels. The binding affinity for the 5-HT_1A 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-HT_1A receptor agonist 8-hydroxy-2-(di-n-propylamino)tetralin revealed an inhibition of cortisol secretion that was independent of 5-HT_1A transcript and protein binding. These results suggest that cortisol plays a role in regulating the 5-HT_1A receptor via GR-mediated pathways; however, further study is necessary to elucidate how and where this inhibition is mediated.