Activation of the Nitric-Oxide System in Nucleus Accumbens Inhibits the Nicotine Reversal Effects upon Ethanol-Induced Amnesia

Document Type : Original Articles


1 Department of Biology, Faculty of Basic Sciences, Islamic Azad University, Lahijan Branch, Lahijan

2 Department of Biology, Faculty of Basic Sciences, Islamic Azad University, Ardabil branch, Ardabil

3 Young Researchers’ Club, Islamic Azad University, Shahr-e-Rey Branch, Tehran, Iran

4 Department of Neuroscience, School of Advanced Medical Sciences and Technologies, Shiraz University of Medical Sciences


The present study investigated the possible involvement of the nucleus accumbens’ (NAc) nitric oxide system in nicotine's reversal effect upon ethanol-induced amnesia. The hypothesis was tested through ethanol state-dependent memory assessment in adult male Wistar rats. Bilateral chronic cannulae were implanted in the NAc and the animals were trained in a step-through type inhibitory avoidance memory task.  The step-through latency was examined 24 h after animals’ training. The pre-training or pre-test intraperitoneal (i.p.) injection of ethanol (0.9 g/kg) decreased the step-through latency, indicating an amnesic effect of the drug. Meanwhile, the pre-test administration of ethanol (0.6 and 0.9 g/kg) could reverse the pre-training ethanol (0.9 g/kg)-induced amnesia, suggesting a state-dependent effect. Similar to ethanol, the pre-test intra-NAc microinjection of nicotine (0.25 and 0.5 µg/rat) alone or nicotine (0.1, 0.25 and 0.5 µg/mouse, intra-NAc) in combination with an ineffective dose of ethanol (0.3 g/kg) could significantly reverse the (pre-training) ethanol-induced memory impairment. The ethanol (0.9 g/kg)-induced amnesia was similarly prevented following the pre-test intra-NAc administration of a nitric oxide synthase (NOS) inhibitor, L-NAME (0.4 and 0.8 µg/rat). Of note, the co-administration of L-NAME (0.04 and 0.08 µg/rat, intra-NAc) with an ineffective dose of nicotine (0.1 µg/rat, intra- NAc) could significantly potentiate the memory-improving effect of nicotine on ethanol-induced amnesia and resembled the effects of pre-test administration of a higher dose of nicotine. Furthermore, while the pre-test intra-NAc injection of L-NAME impaired the memory retrieval by itself, the pre-test intra-NAc administration of L-arginine, a nitric oxide precursor (0.3 and 0.6 µg/rat, intra-NAc), did not exert any effect either alone or in combination with an effective dose of nicotine (0.5 µg/rat, intra-NAc)  on pre-training ethanol-induced memory impairment. Our findings indicated a possible role of the nucleus accumbens’ nitric oxide system in the improving effects of nicotine on ethanol-induced amnesia and the related state-dependent learning. 


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