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Abstract
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Repeated intermittent exposure to morphine may induce sensitization to rewarding effects of this drug. This process (sensitization) plays important role in morphine addiction. Different brain regions and neurotransmitter systems including GABAergic system affect on sensitization. Therefore, the purpose of this study was to assess the effects of modulation of GABAergic systems by isoniazid on the morphine reward sensitization. Methods: Conditioned place preference (CPP) method was used for assessing rewarding effects of drugs. First, CPP induced by morphine (0.5-10 mg/kg, s.c.) or isoniazid (25, 50 and 75 mg/kg i.p.). Sensation to the rewarding effects of morphine induced as follow: on three consecutive days the mice received morphine effective dose (5 mg/kg, s.c.); then after five days interval, induction of CPP commenced with the ineffective dose of morphine (0.5 mg/kg, s.c.). For evaluation of isoniazid effects on morphine reward sensitization, different groups of animals received saline or isoniazid (25, 50 and 75 mg/kg, i.p.) 40 min. before receiving effective doses of morphine (5mg/kg, s.c.). Results: morphine could induce a significant CPP, but isoniazid failed in the induction of CPP. Pretreatment of isoniazid before morphine on the days of sensation induction, could inhibit sensitization to the rewarding effects of morphine, significantly. Conclusion: inhibition of sensitization to rewarding effects of morphine showing promising effects of isoniazid for the treatment of morphine addiction.
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