Recent studies have shown that NMDA receptors are involved in the tolerance and dependence to opioids. In addition, it has been reported that ketamine, dextromethorphan and amantadine have antagonistic activity at NMDA receptors. Therefore, this study was conducted to clarify the effect of these drugs on morphine withdrawal syndrome. Morphine dependence was induced by increasing doses of morphi...

Efficacy is one determinant of whether a drug is an agonist or an antagonist under a particular set of conditions. Relative efficacy among the micro opioid receptor (MOR) ligands buprenorphine, nalbuphine, and morphine was examined in monkeys dependent on morphine (3.2 mg/kg/day) or l-alpha-acetylmethadol (LAAM) (1.0 mg/kg twice daily) and that discriminated naltrexone (0.0178 mg/kg) from salin...

Several lines of evidence have suggested that the glutamatergic system in the nucleus accumbens (NAc) plays an important role in the conditioned rewarding effect of drugs of abuse. In addition, it is recognized that extracellular glutamate is rapidly removed from the synaptic cleft by Na+-dependent glutamate transporters in neurons and glial cells, thereby maintaining physiological levels of gl...

Single injections of morphine induce a state of acute opioid dependence in humans and animals, measured as precipitated withdrawal when an antagonist is administered 4-24 h after morphine. Additional morphine exposure at daily or weekly intervals results in further increases in withdrawal severity, suggesting that acute opioid dependence reflects the early stages in the development of a chronic...

Introduction: Morphine withdrawal syndrome is mediated via several central and peripheral neurological pathways. In the present study we investigated the role of N-methyl-D aspartic acid (NMDA) glutamate receptor on naloxone-induced withdrawal syndrome in morphine-conditioned mice. Materials and Methods: We designed two separate experiments. In experiment one, 30 male NMRI mice were divide...

Opioid agonists such as morphine have been found to exert excitatory and inhibitory receptor-mediated effects at low and high doses, respectively. Ultra-low doses of opioid antagonists (naloxone and naltrexone), which selectively inhibit the excitatory effects, have been reported to augment systemic morphine analgesia and inhibit the development of tolerance/physical dependence. This study inve...

Conventional definitions of drug addiction are focused on characterizing the neurophysiological and behavioral responses of mammals. Although mammalian models have been invaluable in studying specific and complex aspects of addiction, invertebrate systems have proven advantageous in investigating how drugs of abuse corrupt the most basic motivational and neurochemical systems. It has recently b...