Finasteride, a 5alpha-reductase inhibitor, potentiates antinociceptive effects of morphine, prevents the development of morphine tolerance and attenuates abstinence behavior in the rat.
It has been shown that morphine increases 5alpha-reductase enzyme activity in the rat central nervous system; however importance of this finding on morphine analgesia, tolerance and dependence has not been reported. In the present study, we investigated inhibition of 5alpha-reductase enzyme on morphine effects using finasteride. To determine whether the 5alpha-reductase enzyme interact with morphine analgesia, finasteride (5 mg/kg, i.p.) was administrated with morphine (5 and 7 mg/kg, i.p.). The tail-flick test was used to assess the nociceptive threshold, before and 15, 30, 45, 60 and 90 min after drug administration. In tolerance experiments, morphine 20 mg/kg was injected i.p., twice daily for 4 days. The development and expression of dependence were assessed in the naloxone precipitation test 5 days after the morphine (20-30 mg/kg, i.p.) administration. We found that finasteride could potentiate the antinociceptive effect of morphine. In addition, chronic finasteride administration effectively blocked development of tolerance and dependence to morphine. Following chronic morphine administration, single dose injection of finasteride failed to reverse tolerance but prevented naloxone precipitate withdrawal syndrome. Therefore, it was concluded that there is a functional relationship between 5alpha-reductase enzyme and morphine.
Verdi
Javad
J
Department of Physiology and Pharmacology, Kashan University of Medical Sciences, Kashan, Iran.
Ahmadiani
Abolhassan
A
D013741:3-Oxo-5-alpha-Steroid 4-Dehydrogenase / Q000187:drug effects* / Q000378:metabolism; D000701:Analgesics, Opioid / Q000494:pharmacology; D000704:Analysis of Variance; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects / Q000502:physiology; D004347:Drug Interactions; D004361:Drug Tolerance / Q000502:physiology*; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D018120:Finasteride / Q000494:pharmacology*; D008297:Male; D009020:Morphine / Q000494:pharmacology*; D017288:Pain Threshold / Q000187:drug effects*; D051381:Rats; D017208:Rats, Wistar; D019966:Substance-Related Disorders / Q000188:drug therapy / Q000201:enzymology
D000701:Analgesics, Opioid; D004791:Enzyme Inhibitors; D018120:Finasteride; D009020:Morphine; D013741:3-Oxo-5-alpha-Steroid 4-Dehydrogenase