Tolerance and dependence are two main problems that have limited morphine administration as an analgesic drug and they might be as a result of changes in the number and affinity of receptors, dysfunction of adenylate cyclase, impaired coupling between activated µ receptor and K+ channels, and changes in the K+ and Ca2+ channels. There are several reports concerning the role of some of these...

The aim of the present study was to investigate, in vivo, the effect of a Brugmansia arborea extract (BRU), chromatographic fractions (FA and FNA), and isolated alkaloids on the expression and the acquisition of morphine tolerance and dependence. Substances were acutely (for expression) or repeatedly (for acquisition) administered in mice treated with morphine twice daily for 5 or 6 days, in or...

Lithocholic acid (LCA) deposited in human livers always induces drastic pains which need analgesic drug, like morphine to release. Our research showed that LCA can effectively inhibit uridine 5'-diphospho-glucuronosyltransferase 2B7 (UGT2B7) in morphine tolerance-like human normal liver cells, HL-7702, then increase μ-opioid receptor (MOR) and calcium-calmodulin dependent protein kinase IIα (Ca...

Bovine adrenal medulla 22 (BAM22), an endogenous opioid peptide, is one of the cleavage products of proenkephalin A. It potently activates opioid receptors and sensory neuron-specific receptor (SNSR). The present study was aimed at investigating the effect of BAM22 on morphine tolerance. Intrathecal (i.t.) administration of morphine for 7 d produced morphine tolerance in rats. Then the rats wer...

In a rat model of morphine tolerance, we examined the hypotheses that thermal hyperalgesia to radiant heat develops in association with the development of morphine tolerance and that both the development and expression of thermal hyperalgesia in morphine-tolerant rats are mediated by central NMDA and non-NMDA receptors and subsequent protein kinase C (PKC) activation. Tolerance to the analgesic...

The mechanisms by which morphine-induced analgesia and tolerance and physical dependence on morphine arise have been the subject of intense study, and much work has pointed to the involvement of cAMP-mediated events in the neuroadaptive phenomena leading to morphine tolerance and/or dependence. We overexpressed an opioid receptor-stimulatable form of adenylyl cyclase (type 7) in the central ner...

Introduction: Sex differences are observed in the development of tolerance to antinociceptive effect of opioid drugs such as morphine, but the underlying mechanisms remain unclear. Critical role of glutamate in the development and maintenance of opioid tolerance has been reported by many investigators. There are also evidences about interaction between gonadal hormones and neuromodulatory sy...

glutamate has a key role in pain perception and also development of tolerance and dependence to morphine. it has been reported that clavulanic acid affects glutamatergic transmission via activation of glutamate transporter. therefore the present study was aimed to evaluate the possible antinociceptive effect of clavulanic acid and its preventive activity against development of morphine toleranc...

Multiple studies demonstrate that coadministration of N-methyl-D-aspartate (NMDA) receptor antagonists with the opioid agonist morphine attenuates the development of analgesic tolerance. Sex differences in the effects of noncompetitive, but not competitive NMDA receptor antagonists on acute morphine analgesia, have been reported in mice, yet the role of sex in modulation of morphine tolerance b...

Long-term use of opioids is hindered by respiratory depression and the possibility for fatal overdose in drug abusers. This is attributed to higher levels of tolerance that develops against antinociception than to respiratory depression. Identifying important mechanisms that would increase morphine respiratory depression and overdose tolerance could lead to the safer use of opioids. Because pro...