beta-Endorphin-like immunoreactivity in discrete brain regions, spinal cord, pituitary gland and peripheral tissues of U-50,488H-tolerant and -abstinent rats
Bhargava, H.N.; Matwyshyn, G.A.; Rattan, A.K.; Koo, K.L.; Tejwani, G.A.
Journal of Pharmacology and Experimental Therapeutics 268(2): 856-861
1994
ISSN/ISBN: 0022-3565 PMID: 8113998 Document Number: 428707
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 ponsmedulla 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. On the other hand, our previous studies have shown that chronic treatment with morphine decreases the concentration of beta-endorphin in specific tissues. Thus, differences in the levels of beta-endorphin in tissues of rats that received addicting or nonaddicting opioids have been observed.