Activation of the nitric-oxide system in nucleus accumbens inhibits the nicotine reversal effects upon ethanol-induced amnesia

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

[Role of dopamine D2 receptors of the dorsal hippocampus on scopolamine state-dependent memory]

Cholinergic and dopaminergic systems of the brain play an important role in learning and memory. In the present study, we assessed the role of dopamine D2 receptors of the dorsal hippocampus in scopolamine induced amnesia and scopolamine state-dependent memory in adult male rats. Material and In this experimental study 200 adult male Wistar rats were used [25 group]. Rats were anesthetized and then placed in a stereotaxic apparatus. Two stainless-steel cannula were placed 1 mm above CA1 region of dorsal hippocampus. One week later animals were trained in a step-through type inhibitory avoidance task. Pre-training intra-CA1 administration of scopolamine impaired memory retrieval on the test day. The memory impairment induced by pre-training injection of scopolamine was reversed by pre-test administration of scopolamine or quinpirole, which indicated scopolamine induced state-dependent learning and the effect of dopamine D2 receptors of the dorsal hippocampus on this type of learning. Furthermore, memory impairment was produced following pre-test intra-CA1 injection of dopamine D2 receptor antagonist, sulpiride. Pre-test intra-CA1 injection of sulpiride also inhibited scopolamine-induced state-dependent memory. These results suggested that dopaminergic D2 receptors of the dorsal hippocampal CA1 region may play an important role in scopolamine-induced amnesia and scopolamine state-dependent memory

[Influence of nicotine and nitric oxide on anxiety behavior in mice]

Anxiety is a psychological and physiological state characterized by somatic, emotional, cognitive, and behavioral components. Anxiety is considered to be a normal reaction to stress, however excessive anxiety results in anxiety disorder. In this study, we investigated the possible interaction between nicotine and nitric oxide system of the dorsal hippocampus on anxiety-like behavior in mice. This experimental study was performed on 230 male NMRI mice. Mice were anesthetized with intra-peritoneal injection of ketamine hydrochloride, plus xylazine and then placed in a stereotaxic apparatus. Two stainless-steel cannulae were placed in the CA1 region of hippocampus. Nicotine [0.5 mg/kg] was injected intraperitoneally; L-arginine [1 micro g/mouse] and L-NAME 50 ng/mouse was instilled in the cannulae; The elevated plus-maze test was used to test for anxiety-like behaviors. One-way analyses of variance [ANOVAs] followed by LSD test, were used for analysis of the data. Intraperitoneal injection of nicotine or bilateral intra-dorsal hippocampal injections of L-arginine and L-NAME induced anxiogenic effects, p<0.05, p<0.05, p<0.01, respectively. Intraperitoneal injection of lower dose of nicotine [0.1 mg/kg] before different doses of Larginine or L-NAME inhibited anxiogenic effects of L-arginine or L-NAME. It seems that both nitric oxide and nicotinic cholinergic systems play a part in the modulation of anxiety in the dorsal hippocampus of mouse; however the interaction between these two systems is complex

[Effects of mecamylamine [a nicotinic receptor antagonist] on harman induced-amnesia in an inhibitory avoidance test]

Beta-carbolines alkaloids such as harmane have been found in common plant-derived foodstuffs [wheat, rice, corn, barley, grape and mushrooms]. These alkaloids have many cognitive effects including alteration short and long term memory. In the present study, the effect of intra-CA1 injection of the nicotinic receptor antagonist mecamylamine on amnesia induced by harmane was examined in mice. Mice were bilaterally implanted with chronic cannulae in the CA1 regions of the dorsal hippocampus. One week after cannulae implantation, mice were trained in a step-down type inhibitory avoidance task, and were tested 24 h after training to measure step-down latency as a scale of memory. Pre-training or post-training systemic injection of harmane induced amnesia. Pre-testing intra-dorsal hippocampus administration of the high dose of nicotinic receptor antagonist, mecamylamine [4 micro g/mice] also induced amnesia. On the other hand, pre-test intra-CA1 injection of ineffective doses of mecamylamine [0.5, 1 and 2 micro g/mice] fully restored harmane induced amnesia. The present finding in this study indicated that a complex interaction exists between nicotinic receptor of dorsal hippocampus and amnesia induced by Harmane