Effects of NRGC-lesion on the rates of the development of morphine tolerance and dependence in rats

Abstract

The development of tolerance to and dependence on morphine over 1 ?? 8 days treatment with morphine were studied with time in rats in which the nucleus reticularis gigantocellularis (NRGC), including the nucleus reticularis paragigantocellularis, were electrically destructed. The NRGC of SD male rats was bilaterally lesioned (DC, 0.5 mA, 40 sec), and morphine analgesia was estimated by the tail flick method. Morphine analgesia in NRGC-destructed rats (D-rat) was reduced to about 50% of that in sham-operated rats (S-rat). The dose of morphine to produce equi-analgesia increased 2 ?? 21.8 times during 1 ?? 8 days treatment with morphine in S-rat. Throughout this period, ratios of the equi-analgesic dose in D-rat to that in S-rat were almost the same, i.e., the rate of tolerance development to morphine analgesia in D-rat was to the same degree as that in S-rat. Administration of naloxone after 1 ?? 6 days treatment with morphine elicited body weight loss and increase in plasma corticosterone (Pcs), degrees of which were dependent on the dose of naloxone or the period of morphine treatment. No difference in these abstinence signs were detected between S and D-rat, i.e., the rate of development of dependence on morphine in D-rat was to the same degree as that in S-rat. These results suggest that the NRGC participates in the development of morphine analgesia, but does not participate in the development of tolerance to and dependence on morphine.