Repeated exposure to opiates produces analgesic tolerance, which limits their clinical usefulness. Whole-cell voltage-clamped lamina I cells in spinal slices from opiate-tolerant neonatal rats show an increase in miniature, spontaneous, and primary afferent-evoked EPSCs when compared with lamina I cells from opiate-naive rat spinal slices. This increased excitation can be blocked by the NMDA re...

The study of neuronal adaptations induced by opiate drugs is particularly relevant today given their widespread prescription and nonprescription use. Although much is known about the acute actions of such drugs on the nervous system, a great deal of work remains to fully understand their chronic effects. Here, we focus on longer-lasting adaptations that occur in two catecholaminergic brain regi...

Previous work from our laboratory has established that cellular signaling processes of endogenous morphine are mediated by cognate G protein coupled receptor (GPCR) proteins, designated µ(3) and µ(4) opiate receptors. µ(3) and µ(4) opiate receptors are structurally unique "short" 6 transmembrane helical (TMH) domain GPCRs that are selectively responsive to endogenous morphine, not to families o...

A series of 3-O-acyl-6-O-sulfate esters of morphine, dihydromorphine, N-methylmorphinium iodide, codeine, and dihydrocodeine were prepared and evaluated for their ability to bind to mu-, delta-, kappa(1)-, kappa(2)-, and kappa(3)-opiate receptors. Several compounds exhibited good affinity for the mu-opiate receptor. Morphine-3-O-propionyl-6-O-sulfate had four times greater affinity than morphin...

BACKGROUND GPs occupy a pivotal position in relation to providing services to opiate misusers in the UK, and this is now cited to support initiatives in other countries. AIMS To investigate GP involvement in the management of opiate misusers; and to examine the nature of this prescribing of methadone and other opioids. DESIGN GP data collected via self-completion postal questionnaire from a...

Chronic opioid exposure induces neuroadaptative changes in several brain systems. Amongst others the alpha adrenergic system appears to be extremely sensitive to opioid exposure and has, therefore, been proposed to play a key role in opiate withdrawal symptoms. In order to better understand the influence of the noradrenergic system in opioid withdrawal and be able to develop new therapeutic str...

OBJECTIVES This study aimed to describe patterns of major depression (MDD) in a cohort of untreated illicit opiate users recruited from 5 Canadian urban centres, identify sociodemographic characteristics of opiate users that predict MDD, and determine whether opiate users suffering from depression exhibit different drug use patterns than do participants without depression. METHOD Baseline dat...

OBJECTIVE To quantify the effect of opiate substitution treatment in relation to HIV transmission among people who inject drugs. DESIGN Systematic review and meta-analysis of prospective published and unpublished observational studies. DATA SOURCES Search of Medline, Embase, PsychINFO, and the Cochrane Library from the earliest year to 2011 without language restriction. REVIEW METHODS We ...

BACKGROUND Despite intriguing observational cross-sectional data there are no longitudinal studies of opiate related arterial disease. As opiates act via P16INK4A/CDKN2A, and vascular ageing has been thought to be a surrogate for organismal ageing, the subject has far-reaching implications. METHODS Pulse Wave Analysis (PWA) by radial arterial tonometry (SphygmoCor) was performed on control an...