in vivo microdialysis was used to study the effects of morphine on glutamate release from the ventral tegmentum area (vta) in freely moving rats. intraperitoneal (i.p.) injection of acute and repeated morphine at increasing doses significantly enhanced glutamate release. only a minor tolerance developed to this dosage of morphine. ap-s (2-amino-5-phosphonovaleric acid, 0.5 mg/kg i.p.), a nmda r...

Learned associations between environmental cues and morphine use play an important role in the maintenance and/or relapse of opioid addiction. Although previous studies suggest that context-dependent morphine treatment alters glutamatergic transmission and synaptic plasticity in the hippocampus, their role in morphine conditioned place preference (CPP) and reinstatement remains unknown. We inve...

Introduction: There is some evidence supporting the reduced activity of integrins following chronic administration of morphine. This reduction might play a role in morphine tolerance development. Manganese binds to the extracellular domain of integrins and makes them to be activated. The effect of integrins activation using manganese on tolerance development to the analgesic effect of morphine ...

BACKGROUND Alpha 2 (α(2))-adrenoceptor agonists may be useful for their potential to increase or prolong opioid analgesia while attenuating the development of opioid tolerance. The purpose of this study was to investigate the effects of dexmedetomidine and guanfacine (α(2)-adrenoceptor agonists) on morphine analgesia and tolerance in rats. METHODS Adult male Wistar albino rats weighing 195-20...

The radiolabelled opioid receptor binding affinities of morphine and its active metabolite morphine 6-glucuronide at the total mu, mu 1, mu 2 and delta receptors were determined. Morphine 6-glucuronide was found to have a 4-fold lower affinity for the mu 2 receptor (IC50 17 nm and 82 nm for morphine and morphine 6-glucuronide respectively, P = 0.01), the receptor postulated to be responsible fo...

Morphine administered simultaneously to intracerebroventricular (i.c.v.) and intrathecal (i.t.) sites exhibits synergism, with the antinociceptive potency much greater than would be predicted from a simple addition of the potencies of the same dose administered to either site alone. This synergism was quantified in mice using both a fixed dose method, in which the morphine dose at one site was ...

Misra et al. (1971) found that 1 h after a single subcutaneous injection of [N-Me-l4C1morphine into the rat, three radioactive compounds could be extracted from the cerebral cortex, namely free morphine, morphine 3-glucuronide and a ‘non-acid-hydrolysable’ conjugate. The regional and subcellular distribution of morphine and its metabolites in brain after subcutaneous injection has never been st...

Introduction: In order to study the alterations of beta 1 and 2 integrins mRNA level in rat lumbar spinal cord following the induction of chronic pain and its effect on the development of tolerance to morphine analgesia, we examined the level of expression of these genes in the presence of chronic pain, which is an inhibitor of morphine tolerance. We used induction of chronic pain alone and in ...

BACKGROUND To investigate clinical variables such as gestational age, sex, weight, the therapeutic regimens used and mechanical ventilation that might affect morphine requirements and plasma concentrations of morphine and its metabolites. METHODS In a double-blind study, neonates and infants stratified for age [group I 0-4 weeks (neonates), group II > or =4-26 weeks, group III > or =26-52 wee...

Morphine administered nasally to humans as a simple solution is only absorbed to a limited degree, with a bioavailability of the order of 10% compared with intravenous administration. This article describes the development of novel nasal morphine formulations based on chitosan, which, in the sheep model, provide a highly increased absorption with a 5- to 6-fold increase in bioavailability over ...