Differential responses to morphine-induced analgesia in the tail-flick test

Abstract

We compared acute and chronic antinociceptive effects of morphine in animals with high reactivity (HR) vs. low reactivity (LR) to novelty. Antinociception was assessed by tail-flick test. Rats were i.p. injected with either saline or morphine (1.5 or 3 mg/kg) every 12 h for 7 days according to the treatment group. On day 1 of the experiment, LR animals in the 1.5 mg/kg morphine group showed significantly higher tail-flick latency than HR. Moreover, significant tolerance to the antinociceptive effects of morphine at the used doses was observed in LR but not HR animals. However, effects of chronic morphine treatment on tail-flick latency in rat groups with similar morphine-induced acute antinociception were undistinguishable. The difference in tail-flick latency between HR and LR rats observed after acute 1.5 mg/kg morphine injection was eliminated if β-funaltrexamine (3 mg/kg, i.p.) was administered 24 h before the test, an indication that μ opioid receptors are responsible for the difference observed. Studies to anatomically characterize the difference in the acute analgesic effect of morphine in HR vs. LR animals did not however yield any significant difference in μ opioid receptor mRNA levels in locus coeruleus (LC), ventral periaqueductal gray (vPAG), nucleus raphe magnus (NRM) and nucleus reticularis paragigantocellularis (NRPG) between these two groups of animals. In conclusion, our results show that differences in novelty-seeking behavior can predict inter-individual variability in morphine-induced antinociception in rats. Such variability is dependent upon activation of μ opioid receptors, but does not correlate with μ opioid receptor expression in LC, vPAG or ventral medulla.