Role of serotonin in opiate-induced prolactin secretion and antinociception in the developing rat.
Our laboratory has demonstrated previously that the ability of opiates to stimulate prolactin (PRL) release during ontogeny precedes the appearance of a PRL response to serotonergic drugs. The present study tests the hypothesis that opiates stimulate PRL secretion through a serotonergic mechanism in adult rats, but a nonserotonergic mechanism in neonatal rats. Morphine stimulated PRL secretion in adult and neonatal (10-day-old) rats and this increase was blocked with the opiate antagonist naloxone. Ten-day-old or adult rats were pretreated with the serotonin antagonist, cyproheptadine (CYPRO), or the neurotoxin, 5,7-dihydroxytryptamine (5,7-DHT). Both CYPRO and 5,7-DHT attenuated the PRL response to morphine in adult but not neonatal rats. 5,7-DHT decreased serotonin and 5-hydroxyindoleacetic acid substantially in the hypothalamus. When rats were pretreated with 5,7-DHT several weeks before morphine challenge, serotonin depletion was more pronounced, but the PRL response to morphine was not decreased. In addition, the PRL response to 5-hydroxytryptophan was greatly potentiated, suggesting that functional supersensitivity developed in the 5,7-DHT-treated animals. The ability of CYPRO and 5,7-DHT to block the serotonergic component of a different morphine-induced behavior in the neonate was tested using the tail immersion test for analgesia. Morphine produced profound antinociception in the rat pup which was attenuated markedly by 5,7-DHT and CYPRO. These studies demonstrate that opiates mediate their stimulatory effects on PRL release, at least in part, through a serotonergic mechanism in adult rats.(ABSTRACT TRUNCATED AT 250 WORDS)
D015116:5,7-Dihydroxytryptamine / Q000494:pharmacology; D000375:Aging; D000818:Animals; D000831:Animals, Newborn; D003533:Cyproheptadine / Q000494:pharmacology; D006897:Hydroxyindoleacetic Acid / Q000378:metabolism; D007031:Hypothalamus / Q000187:drug effects / Q000254:growth & development*; D009020:Morphine / Q000494:pharmacology*; D010146:Pain / Q000503:physiopathology*; D011388:Prolactin / Q000097:blood / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D012701:Serotonin / Q000378:metabolism*
D003533:Cyproheptadine; D015116:5,7-Dihydroxytryptamine; D012701:Serotonin; D006897:Hydroxyindoleacetic Acid; D009020:Morphine; D011388:Prolactin