Differential Sites of Action of 8OH-DPAT, a 5HT1A Agonist, on ACTH and PRL Secretion in the Rat

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Abstract
We recently obtained evidence that activation of the 5HT1A subtype receptor enhances both plasma ACTH and prolactin (PRL) concentrations in rats. In order to explore the possible neuroanatomical structures involved in this interaction, we examined ACTH and PRL responses to intracerebral infusions of the 5HT1A receptor agonist 8-hydroxy-2-(di-n-propylamino) tetralin (80HDPAT). In addition we also tested in vitro effects of 80HDPAT added to the perifusion medium of pituitary cells or of hypothalamic slices on hormone or neurotransmitter release, respectively. The ACTH response to 80HDPAT (0.1 mg/kg) was decreased after depletion of endogenous 5HT stores by p-chlorophenylalanine (PCPA) treatment. In contrast, the PRL response was markedly increased under that condition. Infusion of 80H-DPAT (1 µg/µl/l5 min) into the dorsal raphe nucleus induced a slow elevation of ACTH release but was ineffective on PRL secretion while infusion of 80HDPAT into the PVN induced a moderate elevation of both ACTH and PRL. After bilateral destruction of the PVN, PRL response to 80HDPAT (0.1 and 0.25 mg/kg) was markedly potentiated. In contrast, PVN-lesioned animals showed a blunted ACTH response to 80HDPAT. Basal or CRF-stimulated ACTH secretion rates from perifused dispersed adenohypophyseal cells were not affected by 80HDPAT but the 5HT1A agonist induced a very slight and transient inhibition of PRL release. 80HDPAT antagonized, in a dose-dependent manner, the K+-induced release of 3H-DA previously taken up in neurons of mediobasal hypothalamic slices. This data suggests that major sites of 5HT1A interaction in PRL and ACTH regulation are located within the CNS and not in the pituitary. ACTH but not PRL control involves presynaptic interactions and autoreceptors in the raphe nuclei as suggested by the blunted response obtained after 5HT depletion by PCPA. Sites of 5HT1A interaction with PRL regulation cannot be definitely identified from our experiments but increased responsiveness to 5HT1A after PVN lesions suggests that this nucleus exerts a negative tone on PRL secretion.

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