The mechanistic similarity between acutely and chronically induced morphine tolerance has been previously proposed but remains largely unexplored. Our experiments examined the modulation of acutely induced tolerance to spinally administered morphine by agonists that affect the N-methyl-D-aspartate receptor and nitric oxide synthase systems. Antinociception was detected via the hot water (52.5 d...

In the adult male Sprague-Dawley rat, a species commonly used to study tolerance to the antinociceptive effects of morphine, approximately 10% of the morphine dose is metabolized to normorphine-3-glucuronide (NM3G). In contrast, NM3G is a relatively minor metabolite of morphine in human urine reportedly accounting for approximately 1% of the morphine dose. To date, the pharmacology of NM3G has ...

Previous studies have demonstrated that prolonged morphine treatment in vivo induces the translocation of delta opioid receptors (deltaORs) from intracellular compartments to neuronal plasma membranes and this trafficking event is correlated with an increased functional competence of the receptor. The mechanism underlying this phenomenon is unknown; however chronic morphine treatment has been s...

The present study was undertaken to investigate the plasticity of calcitonin gene-related peptide (CGRP) in antinociception after morphine tolerance in rats. The hindpaw withdrawal latencies (HWLs) to both thermal and mechanical stimulation increased significantly after intracerebroventricular injection of 2.5 nmol of CGRP in opioid-naive rats, indicating that CGRP produces an antinociceptive e...

Co-administration of 8 opioid agonists at doses which do not produce measurable antinociception were demonstrafed to produce an increase in the antinociceptive potency of morphine in the mouse tail-flick test. In contrast, co-administration of equi-antinociceptive combinations of a 8 agonist plus morphine for three days resulted in the development of less tolerance to morphine antinociceptive a...

Data from rodent antinociception models indicate that N-methyl-D-aspartate (NMDA) receptor antagonists do not produce antinociception alone or potentiate morphine antinociception, but do attenuate the development of morphine tolerance. This study examined the antinociceptive effects of the noncompetitive NMDA receptor antagonist dizocilpine, the competitive NMDA receptor antagonist (-)-6-phosph...

BACKGROUND Morphine and fentanyl are opioid analgesics in wide clinical use that act through the μ-opioid receptor (MOR). However, one limitation of their long-term effectiveness is the development of tolerance. Receptor desensitization has been proposed as a putative mechanism driving tolerance to G protein-coupled receptor (GPCR) agonists. Recent studies have found that tolerance to morphine ...

Several lines of evidence suggest that the N-methyl-D-aspartate receptor (NMDA) and nitric oxide (NO) systems are involved in morphine tolerance. Cyclooxygenase (COX) inhibitors may also play a role in morphine tolerance by interacting with both systems. In the present study, we examined the effects of the COX inhibitors N-(2-cyclohexyloxy-4-nitrophenyl) methanesulphonamide (NS-398, selective C...

Repeated microinjections of morphine into the ventrolateral periaqueductal gray (vPAG) produce tolerance to the antinociceptive effect of morphine [Behav Neurosci 113 (1999) 833]. These results may be a direct effect of morphine on cells within the vPAG or be caused by cues linked to the microinjection procedure (i.e. associative tolerance). The objective of this paper was to determine whether ...

Statins, 3-hydroxy-3-methylglutaryl co-enzyme A (HMG-CoA) reductase inhibitors, are widely used in the management of different diseases beyond their primary indication for lowering cholesterol. Previous studies have demonstrated the neuroprotective effects of simvastatin in different animal models. In the present study, we examined the effects of simvastatin (30, 60, 100 and 300mg/kg, p.o.) on ...