with morphine together with subanalgesic doses of a second opiate did not develop tolerance to the morphine even after seven days of treatment. Although morphine is a favored choice for easing pain, a major drawback of its long-term use is the development of tolerance, which results in reduced analgesic effects upon long-term use. Morphine binds the opioid receptor (MOR), one member of the larg...

Development of tolerance to endotoxin prevents sustained hyper inflammation during systemic infections. Here we report for the first time that chronic morphine treatment tempers endotoxin tolerance resulting in persistent inflammation, septicemia and septic shock. Morphine was found to down-regulate endotoxin/LPS induced miR-146a and 155 in macrophages. However, only miR-146a over expression, b...

N-methyl-D-aspartate (NMDA) receptor antagonists are effective in inhibiting the development of morphine tolerance in adult rats. But NMDA receptors undergo dramatic change during the first few weeks of the postnatal life in the rat, and it is unknown whether NMDA receptor antagonists can inhibit the acquisition of opiate tolerance in the developing organism. Here, we investigated the effects o...

BACKGROUND & OBJECTIVE The mechanism underlying the development of tolerance to morphine is not clearly understood though a number of factors have been implicated. One of the likely factors may be increased activity of anti-opioid peptides like nociceptin (also known as orphanin FQ or N/OFQ). N/OFQ and morphine bind to opioid receptor-like 1 (ORL1) receptor and muopioid receptor respectively. T...

The aim of the present study was to assess the effects of chronic and acute treatment of the essential oil (EO) of Kelussia odoratissima Mozaff. on the development of morphine tolerance and dependence in mice. Mice were rendered tolerant to and dependent on morphine by subcutaneous injection of morphine over a period of 5 days. Tolerance was assessed using the tail-pinch test and withdrawal sig...

In morphine tolerance a key question that remains to be answered is whether mu-opioid receptor (MOPr) desensitization contributes to morphine tolerance, and if so by what cellular mechanisms. Here we demonstrate that MOPr desensitization can be observed in single rat brainstem locus coeruleus (LC) neurons following either prolonged (> 4 h) exposure to morphine in vitro or following treatment of...

A flavor paired with morphine shifted to the right the function relating morphine dose to tail-flick latencies and provoked hyperalgesic responses when rats were tested in the absence of morphine. These learned increases in nociceptive sensitivity were not mediated by alterations in tail-skin temperature. Microinjection of the competitive N-methyl-D-aspartate (NMDA) receptor antagonist D,L-2-am...

The clinical use of morphine to reduce pain is limited because of its drug tolerance, dependence and addiction. In the present study, the tree shrews (Tupaia belangeri chinensis) developed morphine tolerance and chronic morphine dependence by morphine injections with increasing doses (5, 10, 15, 20 mg/kg body weight for 7 days). Meanwhile, the naloxone (1.25 mg/kg body weight)-induced condition...

The effect of oxymatrine on the development of tolerance to the antinociceptive effects of morphine was investigated in rats. The degree of tolerance was assessed using the tail-flick test before and after 6 days of twice daily administration of oxymatrine premorphine (10/20/30 mg/kg). High doses of oxymatrine inhibited the development of morphine tolerance (resembling the effect of 7.5 mg/kg o...

Studies comparing morphine tolerance in males and females are rare, and all studies to date have utilized the rat. To generalize from findings with rats morphine tolerance was investigated in male and female mice using the tail-withdrawal test. Three and 7 days of systemic morphine injections produced significant but unequal rightward shifts in the morphine dose-response curve such that females...