Effects Of Morphine In Animals Research Articles

Does the effect of morphine challenge change on maternal behaviour of dams chronically treated with morphine during gestation and further on during lactation?

Opioids impair the maternal behaviour of rats. The effect of morphine on maternal behaviour in dams treated chronically with morphine during the whole pregnancy and lactation has not been analysed systematically. The aim of the present study was to investigate the possible differences in the disruptive effect of morphine on maternal behaviour following morphine challenges between dams treated chronically with saline or morphine during gestation and postpartum. The antinociceptive action of morphine was also studied in dams. The disruptive effect of morphine on maternal behaviour was not changed as the postpartum period passed. The duration of this effect of morphine lasted for about 2 h. The dose-dependent disruptive effect of acute doses of morphine on maternal behaviour was more marked in the morphine-treated dams, than in the saline-treated ones, indicating a tendency for sensitisation to this effect. A trend for tolerance was observed to the antinociceptive effect of morphine in animals treated daily with morphine during the entire gestational and lactation periods; however, this difference did not reach statistical significance. Our experimental protocol might be a predictive model of human opioid abuse. Sensitisation to the impairing effect of opiates on maternal behaviour may explain why a mother abusing heroin neglects her baby even if she does not experience euphoria.

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 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.

The involvement of nitric oxide in the enhanced expression of μ‐opioid receptors during intestinal inflammation in mice

Intestinal inflammation enhances the potency of mu-opioid receptor (MOR) agonists inhibiting gastrointestinal transit and increases the expression of MOR in mice intestine. The precise mechanisms implicated in the increased expression of MOR during intestinal inflammation are not known. The aim of the study is to evaluate if nitric oxide released during intestinal inflammation could modulate MOR gene expression and affect gastrointestinal transit. Intestinal inflammation was induced by the intragastric administration of croton oil. In CD-1 mice, with and without inflammation, we evaluated the anti-transit effects of morphine in animals treated with NOS inhibitors (L-NAME and L-NIL) and the intestinal levels of iNOS enzyme mRNA. The anti-transit effects of morphine and the expression of MOR mRNA in the gut of wild-type (WT) and iNOS-/- mice were also assessed. Gastrointestinal transit was measured with charcoal meal and mRNA levels determined by real-time PCR. In CD-1 mice, inflammation induced a 10-fold increase (P<0.0001) in iNOS mRNA levels in the gut. The absence of iNOS gene and treatment of CD-1 mice with L-NAME or L-NIL abolished the increased antitransit effects of morphine observed during inflammation. Moreover, although the basal levels of MOR mRNA were similar in WT and iNOS animals (-/-), intestinal inflammation only increased the MOR expression in the gut of WT (P<0.01) but not in iNOS-/- mice. The results suggest that nitric oxide derived from the increased expression of iNOS is implicated in the enhanced effects of morphine and in the upregulation of MOR gene transcription observed during intestinal inflammation.

Treatment of respiratory acidosis with N-allylnormorphine (nalline).

IN 1943 Unna1 first reported the results of animal studies on the antagonistic properties of N-allyl-normorphine (Nalline) to morphine. In recent years, the therapeutic application of these properties has been under investigation in human subjects.2 3 4 Nalline is chemically related to morphine by the substitution of an allyl bromide group in the morphine radical.1 , 5 It counteracts the toxic effects of morphine in animals, especially the depression of respiration, and in some animals it apparently serves as a mild analgesic drug.1 In human beings it not only has no demonstrable analgesic activity in itself but also abolishes the analgesic effects of morphine . . .