Involvement of the 5-HT2 receptor in the 5-HT receptor-mediated stimulation of prolactin release

The present study examined the involvement of 5-HT1C and 5-HT2 receptors in the regulation of prolactin release in the rat. Both the mixed 5-HT2/5-HT1C receptor agonist, 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI), and the preferential 5-HT1C agonist, 2-chloro-6-(1-piperazinyl)pyrazine monohydrochloride (MK-212), elicited a significant increase in plasma prolactin concentration with DOI about 20 times more potent than MK-212. Treatment with DOI, but not with MK-212, induced head twitching in the rat, and this behavior was inhibited by both the mixed 5-HT2/5-HT1C receptor antagonist, ritanserin, and the selective 5-HT2 receptor antagonist, amperozide. DOI-induced prolactin release was also antagonized by ritanserin and amperozide, whereas only ritanserin affected MK-212-induced prolactin release. Furthermore, amperozide did not attenuate d-fenfluramine-elicited prolactin release, which is known to be antagonized by ritanserin. These data suggest that the pharmacological stimulation of prolactin release by DOI is mediated via the 5-HT2 receptor and that the 5-HT1C receptor may be of importance for the physiological regulation of prolactin release.