EFFECTS OF INTRAVENTRICULAR MORPHINE AND ENKEPHALINS ON SCHEDULE-CONTROLLED BEHAVIOR IN NONDEPENDENT, MORPHINE-DEPENDENT AND POST-DEPENDENT RATS

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  • 1 January 1981
    • journal article
    • research article
    • Vol. 219  (2) , 344-351
Abstract
The effects of intraventricular morphine and the metabolically stable enkephalin analogs, D-ala2-leu- and D-ala2-met-enkephalinamide, were compared on food-reinforced operant responding in nondependent, morphine-dependent and postdependent rats. Dependence was induced and maintained by scheduled access to 0.05% morphine solution for 10 min every 6 h for at least 8 wk before testing. In nondependent animals, the lowest dose of the 3 drugs increased responding, whereas higher doses, i.e., 0.3 to 3.0 .mu.g of morphine and 0.1 to 30 .mu.g of the 2 enkephalins, produced graded decreases in responding. On a molar basis, morphine was 2 to 3 times more potent than the enkephalins in decreasing response rate. Naloxone (0.1 and 1.0 mg/kg) competitively antagonized the rate-decreasing effect of all 3 compounds. Chronic morphine treatment produced varying changes in the effects of morphine and the enkephalins. Morphine-dependent rats were tolerant to the rate-decreasing action of morphine, whereas the rate-decreasing effect of D-ala2-met-enkephalinamide was unchanged and that of D-ala2-leu-enkephalinamide was enhanced. Protracted changes in the rate-decreasing effect of morphine, but not the enkephalins, were evident in postdependent animals that were tested 5 wk after withdrawal from morphine. Thus, the effects of morphine and the enkephalins on operant responding are differentially altered as a result of chronic morphine treatment. These results could reflect an allosteric interaction between the neuronal binding sites for morphine and the enkephalins.