Identification of different mechanisms of action for increases of food intake and plasma ACTH concentration following 5-HT1a receptor subtype activation in rat brain.
Both food intake and pituitary ACTH release respond to activation of serotonergic 5-HT1a receptors. However, the effects of the 5-HT1a agonist 8-OH-DPAT on these two paradigms are probably mediated by different mechanisms. Ten micrograms of 8-OH-DPAT were microinjected into the rat paraventricular nuclei (PVN) of the hypothalamus and elicited an elevation of plasma ACTH concentration, but did not change food consumption when compared with controls. On the other hand, microinjection of the same dose of 8-OH-DPAT into the rat dorsal raphé nucleus increased food intake, but failed to alter plasma ACTH levels. This suggests that, among its various possible mechanisms of action, 8-OH-DPAT induces an increase of food intake in rats by activating presynaptic 5-HT1a autoreceptors in the raphé nuclei, where most serotonergic fibers originate, while its effect on plasma ACTH concentration occurs through activation of postsynaptic 5-HT1a receptors in the PVN, where some serotonergic fibers terminate.