thiourea and Substance-Withdrawal-Syndrome

In the present study, the influence of withdrawal from repeated administration of morphine on intra-ventral hippocampal microinjection of histamine-induced anxiety-like behavior was investigated in male Wistar rats. Three days subcutaneous administration of morphine (5-10 mg/kg) followed by five days free of the drug decreased the percentage open arm time and the percentage open arm entries. Intra-ventral hippocampal administration of histamine (2.5-7.5 microg/rat) decreased percentage open arm time and percentage open arm entries. Intra-ventral hippocampal histamine-induced anxiogenic effect was reversed in animals that had previously received the three days morphine (7.5 mg/kg) followed by five days free of the drug. Intra-ventral hippocampal administration of pyrilamine (5-20 microg/rat) or ranitidine (10-40 microg/rat) decreased percentage open arm time and percentage open arm entries. Pyrilamine- or ranitidine-induced anxiogenic effect was not changed in animals that had previously received the three days morphine (7.5 mg/kg) followed by five days free of the drug. Intra-ventral hippocampal injections of clobenpropit increased percentage open arm time. The percentage open arm time and percentage open arm entries were decreased in the morphine-treated animals compared with non-morphine-treated controls. Percentage open arm entries and locomotor activity was reduced with some doses of clobenpropit. It can be concluded that the histamine system is involved in anxiety-like behavior, and repeated injections of morphine followed by five days free of the drugs interact with histamine receptor mechanism.

Topics: Analysis of Variance; Animals; Anxiety; Behavior, Animal; Hippocampus; Histamine; Histamine Antagonists; Imidazoles; Male; Microinjections; Morphine; Motor Activity; Pyrilamine; Ranitidine; Rats; Rats, Wistar; Substance Withdrawal Syndrome; Thiourea

To investigate the effects of clobenpropit and histidine on reinstatement of morphine-induced conditioned place preference (CPP) in rats.. The persistence, extinction and reinstatement of morphine-induced CPP were established.In clobenpropit group three different doses of clobenpropit (2, 5 and 10 microg/rat, i.c.v.) were administered 15 min after morphine (1 mg/kg, i.p.) was injected. In histidine group histidine (100, 200, 500 mg/kg) was given 1 h prior to morphine treatment (1 mg/kg i.p).. The CPP was reinstated by priming injection of 1 mg/kg morphine. Clobenpropit (5, 10 microg/rat) significantly inhabited the reinstatement by a priming dose of morphine-induced CPP compared with the morphine control group; histidine (100, 200, 500 mg/kg) significantly inhibited the reinstatement in a dose-dependent manner.. Clobenpropit and histidine inhibit the revival of morphine-induced CPP in a dose dependent manner, indicating that endogenous histamine may inhibit relapse of morphine to some extent.

Topics: Animals; Conditioning, Operant; Histidine; Imidazoles; Male; Morphine Dependence; Random Allocation; Rats; Rats, Sprague-Dawley; Receptors, Cell Surface; Substance Withdrawal Syndrome; Thiourea

The N-methyl-D-aspartate (NMDA) receptor-nitric oxide (NO) pathway has been linked to opiate withdrawal. Pretreatments with four inhibitors of NO synthase, 7-nitro indazole, 3-bromo-7-nitro indazole, S-methyl-L-thiocitrulline and aminoguanidine, which exhibit different isoform selectivity in vitro, were evaluated for their ability to attenuate signs of naloxone-precipitated morphine withdrawal. In separate experiments, effects of NO synthase inhibitors on blood pressure were measured in naive and morphine-dependent rats. 7-Nitro indazole, 3-bromo-7-nitro indazole and S-methyl-L-thiocitrulline, which are specific inhibitors of the constitutive isoforms, produced dose-dependent reductions of several signs of withdrawal. Blood pressure was unaffected by the indazoles, whereas S-methyl-L-thiocitrulline produced a strong vasoconstrictor response. Aminoguanidine, which selectively inhibits inducible NO synthase, reduced fewer signs of opioid withdrawal, had a lower relative potency and exhibited no vasopressor activity. These data suggest that constitutive isoforms, but not the inducible isoform of NO synthase, have a primary role in NO-mediated processes that modulate the opioid withdrawal syndrome in the rat.

Topics: Analysis of Variance; Animals; Blood Pressure; Citrulline; Disease Models, Animal; Dose-Response Relationship, Drug; Drug Interactions; Enzyme Induction; Enzyme Inhibitors; Guanidines; Heart Rate; Indazoles; Isoenzymes; Male; Morphine; Naloxone; Narcotic Antagonists; Nitric Oxide Synthase; Rats; Rats, Inbred F344; Substance Withdrawal Syndrome; Thiourea