ANALGESIC EFFECTS OF INTRAVENTRICULAR MORPHINE AND ENKEPHALINS IN NONDEPENDENT AND MORPHINE-DEPENDENT RATS

  • 1 January 1982
    • journal article
    • research article
    • Vol. 222  (1) , 190-197
Abstract
The analgesic effects of i.c.v. [intracerebroventricular] morphine and the enzyme-resistant enkephalin analogs, D-Ala2-Leu- and D-Ala2-Met-enkephalinamide, measured in the tail-flick test, were compared in nondependent and morphine-dependent rats. Dependence was induced and maintained by scheduled access to 0.05% morphine solution for at least 8 wk before testing. In the nondependent rats, 1.0-10 .mu.g of each drug injected into the lateral ventricle produced a dose-related increase in analgesia; on a molar basis, morphine was 1.3 (1.0-1.7) times more potent than the enkephalins. Naloxone (0.3 and 1.0 mg/kg) antagonized the analgesic effect of the 3 compounds: the effect of morphine was competitively antagonized, while the interaction between naloxone and the enkephalins did not appear to be competitive. Chronic morphine treatment produced different changes in the analgesic effects of morphine and the enkephalins. In contrast to the tolerance that was observed after s.c. injection of morphine in morphine-dependent rats, the analgesic effect of i.c.v. morphine was enhanced in these animals. The analgesic effect of D-Ala2-Leu-enkephalinamide was enhanced in morphine-dependent animals, while tolerance developed to the effect of D-Ala2-Met-enkephalinamide. The analgesic effects of morphine and enkephalins are differentially altered in the presence of naloxone and in morphine-dependent animals. These results could reflect an allosteric interaction between neuronal binding sites for enkephalins and opiate alkaloids.