The effects of opiates on androgen binding in the forebrain of the rat.

Many heroin addicts and addicts on methadone treatment exhibit sexual dysfunction. It is believed that the primary site of action of the opiates is the hypothalamic-hypophyseal system. Although it is not known how the opiates might alter the hypothalamic-hypophyseal system, it has recently been suggested that the opiates might mimic the steroids by binding to steroid hormone receptors. To test this hypothesis, in vivo autoradiographic studies and in vitro biochemical studies were conducted to see if the binding of androgen to receptors in the central nervous system would be affected by the opiates. In the autoradiographic studies, animals were treated for 10 days with saline, morphine sulfate (50 mg/kg), or methadone hydrochloride (10 mg/kg) and then injected with 3H-dihydrotestosterone (DHT-0.5 microgram/100 grams body weight). The animals were killed 1 hour later and their brains were removed and processed for autoradiography. No significant effects of opiates on nuclear uptake and retention of androgen by the limbic system were found. In the in vitro binding studies, 3H-DHT (5 X 10(9) M) and 3H-estradiol (5 X 10(-9) M) were incubated with cytosol prepared from brain in the presence of varying concentrations of morphine sulfate (10(-3) - 10(-9) M) and methadone hydrochloride (10(-3) - 10(-9) M). Using three different assay systems (LH-20, hydroxylapatite, and sucrose density gradient centrifugation), no consistent effects of opiates on steroid binding to its receptor could be demonstrated. These data along with previously reported data suggest that the opiates do not induce sexual dysfunction by interacting with steroid receptors.