Naltrexone-induced alterations of the distribution of morphine in brain regions and spinal cord of the rat

Abstract

The effects of naltrexone injected intravenously (i.v.) on the pharmacological actions and distribution of i.v. injected morphine in brain regions and spinal cord of male Sprague-Dawley rats were determined. Naltrexone (0.625- and 2.5-mg/kg doses) antagonized the analgesic and hyperthermic effects of morphine (10-mg/kg dose). For distribution studies, naltrexone (0.625- and 2.5-mg/kg doses) was co-administered with morphine via indwelling catheters. Rats were sacrificed at various times after drug injection and the concentration of morphine in brain regions (hypothalamus, hippocampus, cortex, pons and medulla, amygdala, midbrain and corpus striatum), spinal cord and serum was determined by radioimmunoassay. The concentration of morphine in various brain regions was found to be time dependent. Initially, at 5 min, the highest concentration of morphine was found in the hypothalamus and the lowest in the striatum. In cortex and spinal cord, the concentration of morphine was significantly higher in comparison to the other brain regions at 30- and 60-min time points. Co-administration of lower dose of naltrexone (0.625 mg/kg) did not significantly alter the distribution of morphine in brain regions and spinal cord with some exceptions. The higher dose of naltrexone (2.5 mg/kg) increased the concentration of morphine in several brain regions and spinal cord. The ratio of the concentration of morphine in brain region or spinal cord to serum was decreased by naltrexone. It is concluded that naltrexone also alters the distribution of morphine in the central nervous system.