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  • Title: Effect of chronic administration of U-50,488H, a kappa-opioid receptor agonist, on central dopamine D2 receptors of the rat.
    Author: Veeranna, Reddy PL, Bhargava HN.
    Journal: Eur J Pharmacol; 1993 Apr 22; 235(1):23-30. PubMed ID: 8390939.
    Abstract:
    The effect of U-50,488H, a kappa-opiate agonist, induced tolerance and abstinence on the characteristics of dopamine D2 receptors of brain regions and spinal cord was determined in the rat. Male Sprague-Dawley rats were injected with U-50,488H (25 mg/kg i.p) or its vehicle twice a day for 4 days. This procedure resulted in the development of tolerance to the analgesic activity of U-50,488H. The binding characteristics (Bmax and Kd values) of [3H]spiroperidol to dopamine D2 receptors were determined in discrete brain regions (hypothalamus, hippocampus, cortex, pons and medulla, midbrain, corpus striatum and amygdala) and spinal cord of U-50,488H-tolerant and -abstinent rats. Rats labeled as tolerant to U-50,488H were injected with U-50,488H on day 5 and killed 1 h later, whereas those labeled abstinent were killed on day 5 without the injection of the drug. Vehicle-injected rats served as controls. [3H]Spiroperidol bound to brain regions and spinal cord membranes at a single high affinity site. The Bmax and Kd values of [3H]spiroperidol in brain regions and spinal cord of U-50,488H-tolerant and abstinent rats did not differ from their respective vehicle-injected controls. The behavioral responses (total distance travelled, horizontal activity, movement time, total number of movements, number of stereotypic movements, stereotypic time and rest time) to different doses of a selective dopamine D2 receptor agonist, 2-bromo-alpha-ergocryptine (bromocriptine) were also determined in rats treated chronically with U-50,488H.(ABSTRACT TRUNCATED AT 250 WORDS)
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