In vivo effects of serotonergic agents on alpha-melanocyte-stimulating hormone secretion

We used an in vivo pharmacological approach to investigate the potential influence of serotonin (5-HT) on peptide release from the intermediate lobe (IL) of the rat pituitary. Plasma levels of α-melanocyte-stimulating hormone (α-MSH) as well as the ultrastructural appearance of IL cells were used as indicators of IL secretory activity. Plasma β-endorphin levels were also measured to assess the effectiveness of 5-HT-acting drugs. Intraperitoneal administration of 5-hydroxy-L-tryptophan, the synthetic precursor of 5-HT, dramatically elevated the content of 5-HT in the neurointermediate lobe but did not alter plasma titers of α-MSH. Treatment with the 5-HT reuptake blocker fluoxetine elevated plasma levels of β-endorphin but not α-MSH. Administration of the 5-HT₁/5-HT₂ agonist MK-212 produced an elevation in both plasma α-MSH and β-endorphin levels. Quantitative morphometry of IL cells at the ultrastructural level revealed that MK-212 treatment selectively causes depletion of electron-lucent but not electron-dense secretory granules from the cytoplasm of IL cells. Pretreatment with the selective D₂ dopamine agonist apomorphine blocked MK-212-induced release of α-MSH but not β-endorphin. Our results show that manipulation of 5-HT synthesis/reuptake does not affect release of α-MSH, but that direct activation of 5-HT receptors with the nonselective agonist MK-212 stimulates α-MSH release. The ability of apomorphine to block MK-212-induced release of α-MSH suggests a direct antagonism between dopaminergic and serotonergic regulation of α-MSH release.