As a follow-up study to an earlier report that racemic fenfluramine can acutely potentiate the analgesic effects of morphine in humans, we investigated the effects of fenfluramine on the development of tolerance to morphine analgesia in rats. Antinociceptive effect, as measured by the tail-flick latency, was studied over 8 days in rats that received continuous i.v. infusion of 1) 22 mg/kg/day o...

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...

Drug addiction is considered as a chronic, recurrent brain disease characterized by relapse. Repeated exposure to certain drugs, such as morphine, can produce deleterious sequelae, such as drug dependence, tolerance and compulsive drug seeking. In the present study, we investigated the dependence and psychological craving for morphine in rats using the conditioned place preference (CPP) paradig...

BACKGROUND AND PURPOSE The effects of ketamine in attenuating morphine tolerance have been suggested to result from a pharmacodynamic interaction. We studied whether ketamine might increase brain morphine concentrations in acute coadministration, in morphine tolerance and morphine withdrawal. EXPERIMENTAL APPROACH Morphine minipumps (6 mg·day(-1) ) induced tolerance during 5 days in Sprague-D...

previous studies have shown that the extract of papaver rhoeas reduces morphine dependence, locomotor activity and reward. in present study, the effects of hydro-alcohol extract of papaver rhoeas on the tolerance to analgesic effects of morphine in mice have been investigated using tail flick method. subcutaneous (s.c.) administration of morphine (1, 2, 5 and 10 mg/kg) induced analgesia. howeve...

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...

Morphine and other mu opioids mimic and/or modulate the discriminative stimulus (DS) effects of cocaine, possibly reflecting mutual stimulation of mesolimbic dopamine activity. Less is known about the capacity of cocaine and related stimulants to modulate the DS effects of morphine. The present study investigated the effects of cocaine, amphetamine, and reference drugs, administered alone and w...

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...