Differential responses to morphine-induced analgesia in the tail-flick test.
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 3mg/kg) every 12h for 7 days according to the treatment group. On day 1 of the experiment, LR animals in the 1.5mg/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 1.5mg/kg morphine injection was eliminated if beta-funaltrexamine (3mg/kg, i.p.) was administered 24h before the test, an indication that mu 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 mu 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 mu opioid receptors, but does not correlate with mu opioid receptor expression in LC, vPAG or ventral medulla.
Cecchi
M
M
Molecular and Behavioral Neuroscience Institute, The University of Michigan School of Medicine, Ann Arbor, MI 48109-0720, USA. cecchi@umich.edu
Capriles
N
N
Watson
S J
SJ
Akil
H
H
D000698:Analgesia; D000701:Analgesics, Opioid / Q000494:pharmacology*; D000704:Analysis of Variance; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D005786:Gene Expression Regulation / Q000187:drug effects; D008297:Male; D009020:Morphine / Q000494:pharmacology*; D009043:Motor Activity / Q000187:drug effects; D009271:Naltrexone / Q000031:analogs & derivatives / Q000494:pharmacology; D009292:Narcotic Antagonists / Q000494:pharmacology; D010147:Pain Measurement / Q000187:drug effects*; D010487:Periaqueductal Gray / Q000187:drug effects / Q000378:metabolism; D011903:Raphe Nuclei / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D017450:Receptors, Opioid, mu / Q000235:genetics / Q000378:metabolism; D013997:Time Factors
D000701:Analgesics, Opioid; D009292:Narcotic Antagonists; D017450:Receptors, Opioid, mu; D009271:Naltrexone; C024524:beta-funaltrexamine; D009020:Morphine