GENOTYPE-DEPENDENT BEHAVIORAL SENSITIVITY TO MU-OPIATE VS KAPPA-OPIATE AGONISTS .2. ANTINOCICEPTIVE TOLERANCE AND PHYSICAL-DEPENDENCE

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  • 1 January 1984
    • journal article
    • research article
    • Vol. 231  (2) , 312-316
Abstract
Antinociceptive tolerance, cross-tolerance and an expression of physical dependence to morphine (MRP) and (.+-.)-ethylketacyclazocine (EKC) were quantitatively compared using 2 inbred strains of mice. The measure of analgesia was the area of a time-response curve (escape reaction, 52.degree. C heated plate). (-)-EKC was 1.5 to 1.8 times more potent than MRP in both C57B1.6J (C57) and DBA/2J (DBA) mice. The latter strain was significantly more sensitive to both analgesics. Paradoxically, after an identical dose, the MRP content in DBA plasma, brain and spinal cord was only 56 to 73% of that in C57 tissues. Mice rendered tolerant to MRP (32 mg/kg s.c./b.i.d. [twice daily]/1 wk) exhibited equivalent cross-tolerance to EKC. In contrast, mice made tolerant to EKC (32 mg/kg s.c./b.i.d./1 wk) retained substantial sensitivity to MRP. Comparisons between drugs and strains indicate that analgesic tolerance and physical dependence did not develop in parallel.