TY - JOUR T1 - beta-Endorphin-like immunoreactivity in discrete brain regions, spinal cord, pituitary gland and peripheral tissues of U-50,488H-tolerant and -abstinent rats. JF - Journal of Pharmacology and Experimental Therapeutics JO - J Pharmacol Exp Ther SP - 856 LP - 861 VL - 268 IS - 2 AU - H N Bhargava AU - G A Matwyshyn AU - A K Rattan AU - K L Koo AU - G A Tejwani Y1 - 1994/02/01 UR - http://jpet.aspetjournals.org/content/268/2/856.abstract N2 - The effect was determined of trans-3,4-dichloro-N-methyl-N-[2-(1-pyrrolidinyl)cyclohexyl]benzene- acetamide methane sulfonate (U-50,488H), a kappa opioid agonist, -induced tolerance dependence and abstinence on the levels of beta-endorphin in discrete brain regions, spinal cord, pituitary gland, plasma and peripheral tissues of male Sprague-Dawley rats. The brain regions examined were hypothalamus, hippocampus, amygdala, midbrain, corpus striatum, pons-medulla and cortex. The peripheral tissues included kidneys, spleen, adrenals and heart. Rats were made tolerant dependent on U-50,488H by intraperitoneal injections of the drug (25 mg/kg) twice a day for 4 days. Vehicle-injected rats served as controls. Rats that were labeled as tolerant dependent were injected with 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 analgesic and hypothermic effects of U-50,488H developed, as evidenced by a decrease in the intensity of responses in chronic U-50,488H-treated compared with chronic vehicle-treated rats. In U-50,488H-tolerant rats, the concentration of beta-endorphin was increased in hippocampus, corpus striatum, pituitary gland, plasma, kidneys and adrenals compared with vehicle-injected controls. In U-50,488H-abstinent rats, the concentration of beta-endorphin was increased in pons-medulla and amygdala, whereas the concentration of beta-endorphin did not change in the pituitary gland, plasma and peripheral tissues. In general, chronic treatment with a kappa opioid agonist results in increases in the concentration of beta-endorphin in specific tissues.(ABSTRACT TRUNCATED AT 250 WORDS) ER -