BETA-ENDORPHIN-LIKE IMMUNOREACTIVITY IN DISCRETE BRAIN-REGIONS, SPINAL-CORD, PITUITARY-GLAND AND PERIPHERAL-TISSUES OF U-50,488H-TOLERANT AND U-50,488H-ABSTINENT RATS

The effect was determined of trans-3,4-dichloro-N-methyl-N-[2-(1 -pyrr olidinyl)cyclohexyl]benzene-acetami methane sulfonate (U-50,488H), a k appa opioid agonist, -induced tolerance dependence and abstinence on t he levels of beta-endorphin in discrete brain regions, spinal cord, pi tuitary gland, plasma and peripheral tissues of male Sprague-Dawley ra ts. The brain regions examined were hypothalamus, hippocampus, amygdal a, midbrain, corpus striatum, pons-medulla and cortex. The peripheral tissues included kidneys, spleen, adrenals and heart. Rats were made t olerant dependent on U-50,488H by intraperitoneal injections of the dr ug (25 mg/kg) twice a day for 4 days. Vehicle-injected rats served as controls. Rats that were labeled as tolerant dependent were injected w ith U-50,488H (25 mg/kg) on day 5 and killed 1 hr later, whereas those labeled as abstinent were killed without injection of the drug. Rats serving as controls were injected with the vehicle. Tolerance to the a nalgesic and hypothermic effects of U-50,488H developed, as evidenced by a decrease in the intensity of responses in chronic U-50,488H-treat ed compared with chronic vehicle-treated rats. In U-50,488H-tolerant r ats, the concentration of beta-endorphin was increased in hippocampus, corpus striatum, pituitary gland, plasma, kidneys and adrenals compar ed with vehicle-injected controls. In U-50,488H-abstinent rats, the co ncentration of beta-endorphin was increased in pons-medulla and amygda la, whereas the concentration of beta-endorphin did not change in the pituitary gland, plasma and peripheral tissues. In general, chronic tr eatment with a kappa opioid agonist results in increases in the concen tration of beta-endorphin in specific tissues. On the other hand, our previous studies have shown that chronic treatment with morphine decre ases the concentration of beta-endorphin in specific tissues. Thus, di fferences in the levels of beta-endorphin in tissues of rats that rece ived addicting or nonaddicting opioids have been observed.