ABSTRACT
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 microg/rat] alone or nicotine [0.1, 0.25 and 0.5 microg/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 microg/rat]. Of note, the co-administration of L-NAME [0.04 and 0.08 microg/rat, intra-NAc] with an ineffective dose of nicotine [0.1 micro g/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 micro g/rat, intra-NAc], did not exert any effect either alone or in combination with an effective dose of nicotine [0.5 micro g/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