Adrenaline release by the 5-HT1A receptor agonist 8-OH-DPAT is partly responsible for pituitary activation

In male Wistar rats the effect of adrenalectomy on pituitary activation by the 5-HT1A receptor agonist. 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT), was studied. Rats were injected intravenously with 8-OH-DPAT (0.10 mg/kg) in their home cages. Blood samples were withdrawn from freely moving cannulated rats for determination of plasma adrenaline and plasma adrenocorticotropin hormone (ACTH). Adrenalectomized rats showed almost no measurable amounts of plasma adrenaline, but these animals had elevated baseline plasma ACTH levels as compared to sham-operated rats. 8-OH-DPAT treatment led to a large plasma adrenaline response in the sham-operated animals, which was abolished after adrenalectomy. The plasma ACTH response to 8-OH-DPAT was significantly diminished in the adrenalectomized rats as compared to sham animals. This blunted ACTH response in adrenalectomized rats, however, was still considerable in magnitude. The present data thus indicate that the plasma ACTH response to 8-OH-DPAT is due to at least two different mechanisms. First, via 5-HT1A receptor-mediated adrenaline release, which may consequently stimulate the pituitary. Second, a direct action of 8-OH-DPAT on hypothalamic 5-HT1A receptors is assumed, independent of peripheral adrenaline release.