Fentanyl stimulates prolactin release through mu-opiate receptors, but not the serotonergic system.
Both serotonin (5-HT) and opiates exert a stimulatory effect on PRL secretion. Some evidence suggests that the action of opiates may be elicited through serotonergic neurons. We tested this hypothesis in the present study by evaluating the effect of perturbation of the serotonergic system on PRL secretion induced by fentanyl, a potent morphine-like analgesic. Female Sprague-Dawley rats ovariectomized for 3 weeks and given polyestradiol phosphate (0.1 mg/rat) for 1 week were used in the study. Fentanyl, at a dose of 20 micrograms/rat, induced significant PRL secretion that peaked at 10 min and lasted for more than 30 min. Pretreatment with naloxone (0.5 mg/kg BW, ip) did not block the acute phase of PRL secretion, but significantly lowered the PRL level at 30 min. Fentanyl at a smaller dose (5 micrograms/rat, iv) still induced significant PRL release 10, but not 30, min after injection. This effect was significantly blocked by pretreatment with the same dose of naloxone. On the other hand, whereas animals pretreated with ketanserin or LY53857 (both at a dose of 5 mg/kg BW, ip), two specific 5-HT2 receptor antagonists, had no effect on fentanyl-induced PRL secretion, the same treatment significantly blocked 5-HT-induced PRL secretion. Likewise, pretreatment with p-chlorophenylalanine (250 mg/kg BW, ip), a 5-HT synthesis inhibitor, for 2 days had no effect on the action of fentanyl, while 5-HT-induced PRL secretion was significantly augmented. We conclude that fentanyl acts through mu-opiate receptors to stimulate PRL secretion in a process that does not involve the serotonergic system.
Pan
J T
JT
Institute of Physiology, National Yang-Ming Medical College, Taipei, Taiwan, Republic of China.
Teo
K L
KL
D000818:Animals; D004305:Dose-Response Relationship, Drug; D004873:Ergolines / Q000494:pharmacology; D005260:Female; D010134:Fenclonine / Q000494:pharmacology; D005283:Fentanyl / Q000494:pharmacology*; D007650:Ketanserin / Q000494:pharmacology; D011388:Prolactin / Q000037:antagonists & inhibitors / Q000378:metabolism*; D051381:Rats; D011957:Receptors, Opioid / Q000502:physiology*; D012701:Serotonin / Q000378:metabolism* / Q000494:pharmacology; D012702:Serotonin Antagonists / Q000494:pharmacology
D004873:Ergolines; D011957:Receptors, Opioid; D012702:Serotonin Antagonists; D012701:Serotonin; D011388:Prolactin; D007650:Ketanserin; C032663:LY 53857; D010134:Fenclonine; D005283:Fentanyl