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...

Objective(s): Central nucleus of amygdala (CeA) is the most important region for morphine-induced reward, and GABAergic system plays an important role on morphine reinforcement. The influence of CeA administration of GABAB receptor agonist and antagonist on the expression and acquisition of morphine-induced incentive tolerance using conditioned place preference (CPP) paradigm was investigated i...

Introduction: Topiramate is an anti-convulsant drug, which produces its effects via glutamate metabotropic receptors inhibition and/or GABA receptor excitation. In the present study, attempts were made to investigate the effects of topiramate on the tolerance to morphine-induced analgesia activity in male NMRI mice (20-30 g). Methods: Hot plate method was chosen for the study. First of all t...

The effect of NMDA (N-methyl-D-aspartate) receptor antagonists on tolerance to morphine antinociception was investigated in mice. Daily subcutaneous administration of 50 mg/kg of morphine hydrochloride for three days induced tolerance to different (3,6 and 9 mg/kg) test doses of morphine. The tolerance obtained was decreased by pretreatment of animals with single or repeated doses of compe...

Repeated administration of the relatively low-efficacy micro-opioid receptor agonist morphine induces tolerance to its antinociceptive effects. High-efficacy agonists such as D-Ala2NMePhe4,Gly-ol5 (DAMGO) have been shown to be less effective at producing tolerance, suggesting that different neural mechanisms underlie tolerance to these agonists. However, the correlation between agonist efficacy...

Introduction: Several researches have reported that stress is able to inhibit the development of morphine tolerance via activating of Hypothalamic-Pituitary-Adrenal (HPA) axis. In the present study we tried to examine the effect of epinephrine, the product of adrenal medulla, on the development of morphine tolerance. Methods: Analgesic tolerance was induced by intrathecal (i.t.) injection of...

OBJECTIVES Central nucleus of amygdala (CeA) is the most important region for morphine-induced reward, and GABAergic system plays an important role on morphine reinforcement. The influence of CeA administration of GABAB receptor agonist and antagonist on the expression and acquisition of morphine-induced incentive tolerance using conditioned place preference (CPP) paradigm was investigated in t...

Respiratory depression is the major cause of death in opioid overdose. We have previously shown that prolonged treatment of mice with morphine induces profound tolerance to the respiratory-depressant effects of the drug (Hill et al., 2016). The aim of the present study was to investigate whether tolerance to opioid-induced respiratory depression is mediated by protein kinase C (PKC) and/or c-Ju...

The aim of this study was to investigate the effect of ketamine and midazolam on preventing the development of morphine tolerance and dependence and withdrawal syndrome in mice. In the present study different groups of mice were received morphine (50 mg/kg, s.c.), morphine (50 mg/kg, s.c.) + ketamine (25, 50, 75 mg/kg, i.p.) , morphine (50 mg/kg , s.c.) + midazolam (0.5, 1, 2 mg/kg, i.p.) , mor...

long-term exposure to opiates induces physical dependence and tolerance. the main goal of this study was to evaluate the effects of dextromethorphan and midazolam and their combination on morphine tolerance and dependence in mice. different groups of mice were rendered randomly and received morphine (50 mg/kg, sc), morphine (50 mg/kg, sc) + dextromethorphan (25,50 or 75 mg/kg, ip), morphine (50...