BACKGROUND Chronic morphine exposure creates dependence and, upon cessation, withdrawal symptoms. Studies indicate the phosphodiesterase type 5 (PDE5) inhibitor sildenafil may provide centrally mediated benefits against withdrawal, and therefore, this study evaluated morphine withdrawal signs in dependent mice with and without sildenafil treatment. METHOD Dependence was induced by repeated tr...

To define the roles of the calmodulin-stimulated adenylyl cyclases (AC1 and AC8) in morphine-induced analgesia, tolerance, physical dependence, and conditioned place preference, we used mice having targeted disruptions of either the AC1 or AC8 genes or both genes [double knockout mice (DKO)]. Mice lacking either AC1 or AC8 genes or DKO did not differ from wild-type mice in short-term antinocice...

cal Hazards, Faculty of Pharmaceutical Sciences, University of Tokyo, Bunkyo-ku, Tokyo. The mechanism of the development of tolerance to and of physical dependence on morphine has been examined from a wide range of aspects. One of the approaches is to investigate the participation of brain biogenic amines in the actions of morphine. In 1954 Vogt (1) found a reduction of the content of hypothala...

This study was designed to examine the effect of environmental enrichment during morphine dependency and withdrawal on the severity of naloxone-precipitated withdrawal signs, anxiety, and depressive-like behaviors and voluntary morphine consumption in morphine-dependent rats. The rats were injected with bi-daily doses (10 mg/kg, 12 h intervals) of morphine for 14 days following rearing in a sta...

Morphine is an exceptionally effective analgesic whose utility is compromised by the development of tolerance and dependence to the drug. Morphine analgesia and dependence are mediated by its activity at the mu opioid peptide (MOP) receptor [1]. The MOP receptor is activated not only by morphine, but also by other opiate drugs such as methadone and endogenous opioids such as endorphins. Morphin...

The main aim of this study was to evaluate the effects of dextromethorphan and midazolam and their combination on morphine tolerance and dependence in mice. In the present study, different groups of mice were rendered randomly and received morphine (50 mg kg(-1), s.c.), morphine (50 mg kg(-1), s.c.) + Dextromethorphan (25, 50 and 75 mg kg(-1), i.p.), morphine (50 mg kg(-1), s.c.) + midazolam (0...

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...

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...