To the Editor: The use of N-methyl-D-aspartate (NMDA) receptor antagonists to decrease opioid side effects, potentiate opioid actions, and decrease the development of tolerance has been a topic of substantial interest over the last decade. The pioneering work by Trujillo and Akil suggested that tolerance to opioids could be prevented by the non-competitive NMDA receptor antagonist MK-801.1 Subs...

The cross-tolerance technique was used to analyze the receptor mechanisms of analgesia induced by electroacupuncture (EA) of 2 Hz, 100 Hz, or 2-15 Hz. (1) Rats were given EA stimulation of 2 Hz, 100 Hz and 2-15 Hz for 30 min with 30 min intervals successively. The percentage increase in tail-flick latency (TFL) was taken to indicate the intensity of EA analgesia. Rats made tolerant to repeated ...

Opioid drugs, such as morphine, are among the most effective analgesics available. However, their utility for the treatment of chronic pain is limited by side effects including tolerance and dependence. Morphine acts primarily through the mu-opioid receptor (MOP-R) , which is also a target of endogenous opioids. However, unlike endogenous ligands, morphine fails to promote substantial receptor ...

We investigated the effect of long-term administration of opioid antagonists on the regulation of prodynorphin gene expression in rat brain. Intracerebroventricular (i.c.v.) injections for seven days of nor-binaltorphimine (nor-BNI), the highly selective kappa opioid antagonist, naloxone and its longer acting analog naltrexone, both relatively selective antagonists for the mu opioid receptor, m...

Zhou, Q. 2001, The Impact of Substance P (SP) N-Terminal Metabolite SP1-7 in Opioid Tolerance and Withdrawal. Acta Univ. Ups. Comprehensive Summaries of Uppsala Dissertations from the Faculty of Pharmacy 260. 60 pp. Uppsala. ISBN 91-554-5174-8. The heptapeptide SP1-7, a metabolite of the neuroactive peptide substance P (SP), is suggested to play a role in opioid addiction and memory function. T...

Antagonists of the NMDA type of excitatory amino acid (EAA) receptor attenuate or reverse the development of tolerance to the analgesic effects of the mu opioid agonist morphine, the delta-1 opioid agonist DPDPE but not the kappa-1 agonist U50,488H or the kappa-3 agonist naloxone benzoylhydrazone. The role of the AMPA subtype of EAA receptor in analgesic tolerance was examined using LY293558, a...

BACKGROUND In general, opioids that induce the recycling of mu-opioid receptors (MORs) promote little desensitization, although morphine is one exception to this rule. While morphine fails to provoke significant internalization of MORs in cultured cells, it does stimulate profound desensitization. In contrast, morphine does promote some internalization of MORs in neurons although this does not ...

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...