Single opioid administration modifies gonadal steroids in both the CNS and plasma of male rats.
While morphine remains one of the most widely used opioids for the treatment of painful conditions, other opioids are also commonly employed. Because of the interactions between opioids and gonadal hormones, in particular opioid-induced hypogonadism, this study investigated the effects of widely used opioids on plasma testosterone and estradiol levels and brain testosterone levels in male rats. Animals were s.c. injected with two concentrations of morphine (5 or 10 mg/kg), fentanyl (0.05 or 0.1 mg/kg), tramadol (10 or 40 mg/kg), buprenorphine (0.05 or 0.1 mg/kg) or saline (0.7 ml/kg). Four or 24 h after treatment, the rats were deeply anesthetized to collect blood samples from the abdominal aorta and to perfuse the brains with saline. Plasma and brain hormone levels were measured by radioimmunoassay. In rats studied 4 h after treatment, all the opioids except tramadol 10 mg/kg decreased plasma testosterone in comparison with saline administration. At the same time, plasma estradiol levels were lower than control in the groups treated with the low doses of morphine, tramadol and buprenorphine, while estradiol remained at control levels in the other groups. Twenty-four hours after treatment, plasma testosterone levels were different (higher) than control in the animals treated with the low doses of morphine, fentanyl and buprenorphine. Estradiol was lower than control in the low dose groups, while the high doses did not produce any changes with respect to control. Four hours after treatment, brain testosterone was drastically decreased in all groups except buprenorphine, in which it remained at control levels. All groups returned to control levels at 24 h after treatment. In conclusion, opioids exert important effects on plasma and CNS sex hormone levels. The different magnitude and time-course of the effects of the different opiates on testosterone and estradiol levels are likely due to their different mechanism of action.
Pain and Stress Neurophysiology Laboratory, Neuroscience and Applied Physiology Section, Department of Physiology, University of Siena, Via Aldo Moro, 2, 53100 Siena, Italy.
I
I
Ceccarelli
A M
AM
De Padova
P
P
Fiorenzani
C
C
Massafra
A M
AM
Aloisi
D000701:Analgesics, Opioid / Q000008:administration & dosage / Q000009:adverse effects*; D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000378:metabolism* / Q000503:physiopathology; D001923:Brain Chemistry / Q000187:drug effects / Q000502:physiology; D002047:Buprenorphine / Q000009:adverse effects; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation / Q000187:drug effects / Q000502:physiology; D004958:Estradiol / Q000378:metabolism; D005283:Fentanyl / Q000009:adverse effects; D012739:Gonadal Steroid Hormones / Q000097:blood / Q000378:metabolism*; D007006:Hypogonadism / Q000139:chemically induced / Q000378:metabolism / Q000503:physiopathology; D008297:Male; D009020:Morphine / Q000009:adverse effects; D009490:Neurosecretory Systems / Q000187:drug effects* / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar; D013737:Testis / Q000378:metabolism*; D013739:Testosterone / Q000097:blood / Q000378:metabolism; D014147:Tramadol / Q000009:adverse effects
D000701:Analgesics, Opioid; D012739:Gonadal Steroid Hormones; D014147:Tramadol; D013739:Testosterone; D002047:Buprenorphine; D004958:Estradiol; D009020:Morphine; D005283:Fentanyl