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

[Modulation of muscimol state-dependent learning by alpha 1-adrenergic receptors of the dorsal hippocampus]

Adrenergic and GABAergic systems of the brain play important roles in learning and memory. Previous studies have shown that morphine, histamine and lithium can induce state dependent learning. In the present study we evaluated, the effects of alpha 1-adrenergic receptor of CA1 on muscimol state-dependent learning in mice. Material and In this experimental study adult male NMRI mice were used. The animals were anaesthetized and bilateral implantation of cannula in the CA1 regions of the dorsal hippocampus was performed by using stereotaxic method. Seven days after recovery, we used inhibitory avoidance task for behavioral testing. Data were analyzed by Kruskal-Wallis nonparametric one-way analysis of variance followed by Mann-Whitney test. Pre-training or pre-test intra-CA1 injection of muscimol impaired inhibitory avoidance memory on the test day [P<0.01]. Pre-test injection of muscimol reversed the memory impairment induced by pre-training muscimol injection [P<0.001]. Pre-test intra-CA1 injection of phenylephrine also reversed pre-training muscimol induced amnesia [P<0.01]. Pre-test intra-CA1 injection of prazosin 2 min before administration of the effective dose of muscimol inhibited muscimol state dependent memory [P<0.01]. It can be concluded that the alpha 1-adrenergic receptors of the CA1 may play an important role in the muscimol state dependent learning, on the test day

[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

[Assessment of effects of alpha2-adrenoceptor agonists and antagonists in dorsal hippocampus on muscimol state-dependent memory]

Adrenergic and GABAergic systems of the brain play an important role in memory and learning. According to results of studies, morphine, histamine, and lithium induce state-dependent learning. This study was conducted aiming at assessing the effects of alpha2-adrenergic receptors of CA1 on muscimol state-dependent learning. In this study, Clonidine as agonist and yohimbine as antagonist of alpha2-adrenergic receptor, muscimol as agonist of GABAA receptor and step-through inhibitory avoidance task as a model of learning were used for memory assessment. The data analyzed using one-way analysis of variance, t-test, and Mann-Whitney test. In all statistical assessments, p<0.05 was considered as significance level in the comparison of the groups. Pre-test intra-CA1 injection of muscimol [1.2microg/mice] impaired inhibitory avoidance memory on the test day [p<0.01]. Pre-test injection of muscimol [0.06 and 1.2microg/mice] reversed the memory impaired under pre-training muscimol [1.2microg/mice]; so, muscimol can induce state-dependent learning [p<0.001]. Pre-training injection of Clonidine [0.6 and 1.2microg/mice] also reversed pre-training muscimol [1.2microg/mice, intra-CA1] induced amnesia [p<0.01]. Also pre-test intra-CA1 injection of yohimbine [1.2 and 2.4microg/mice] 2 minutes before administration of effective dose of muscimol inhibited muscimol state-dependent memory [p<0.01]. Overall, It can be conceded that alpha2-adrenergic receptors of dorsal hippocampus have an important role in muscimol state-dependent learning on the test day

[Evaluation of the interaction between NMDA receptors of nucleus accumbens and muscarinic receptors in memory]

Whereas studies have indicated the interaction between NMDA and cholinergic systems, this study was performed with the aim of determining the role of NMDA receptors in the nucleus accumbens [NAc] in scopolamine-induced amnesia. In this study, at first rats were anesthetized with intra-peritoneal injection of ketamine hydrochloride plus xylazine, and then placed in a stereotaxic apparatus. Two stainless-steel cannulas were placed 2mm above nucleus accumbens shell. All animals were allowed to recover for one week, before beginning the behavioral testing. Then, animals were trained in a step-through type inhibitory avoidance task. The drugs were injected after successful training and before testing. The animals were tested 24h after training, and the step-through latency time was measured as the memory criterion in male Wistar rats. One-way analysis of variance and Tukey's test were used for analysis of the data. p<0.05 was considered statistically significant. Intra-nucleus accumbens [intra-NAc] injection of scopolamine or NMDA caused impairment in memory in rats. Although, co-administration of an ineffective dose of NMDA with an ineffective dose of scopolamine had no significant effect on memory performance, effective doses of NMDA prevented the amnesic effect of scopolamine on inhibitory avoidance memory. On the other hand, intra-NAc injection of NMDA receptor antagonist, i.e., MK-801 caused no change in memory performance by itself, and its co-administration with an effective dose of scopolamine could not prevent the impairing effect of the latter drug. The finding of this study indicated that NMDA receptors in the nucleus accumbens are involved in the modulation of scopolamine-induced amnesia

Modulation of WIN55, 212-2 state-dependent memory by alpha2-adrenergic receptors of the dorsal hippocampus

An overlapping distribution of alpha2-adrenergic receptors with cannabinoid receptors has been reported in certain brain structures such as the dorsal hippocampus. Thus, functional interactions between cannabinoid and alpha2-adrenergic systems in cognitive control seem possible. In the present study, we examine the possible role of alpha2-adrenergic receptors of the dorsal hippocampus on WIN55.212-2 state-dependent learning. Adult male Wistar rats were bilaterally implanted with chronic cannulae in the CA1 regions of their dorsal hippocampi trained in a step-down type inhibitory avoidance task and tested 24 hr after training, to measure step-down latency. Post-training or pre-test intra-CA1 administration of the cannabinoid receptor agonist, WIN 55,212-2 [0.25 and 0.5microg/rat] induced amnesia. Amnesia produced by post-training WIN55,212-2 [0.5 microg/rat] was reversed by pre-test administration of WIN55,212-2, that was due to a state-dependent effect. Pre-test intra-CA1 microinjections of clonidine [0.25, 0.5 and 1 microg/rat] or yohimbine [0.5, 0.75, and 1 MQ/rat] did not affect memory retrieval per se. Pre-test intra-CA1 administration of clonidine [0.5 and 1 micro9/rat] or clonidine [0.25, 0.5, and 1 microg/rat] with an ineffective dose of WIN 55,212-2 [0.25 microg/rat] reversed post-training WIN55,212-2 [0.5 microg/rat,intra-CA1] induced memory impairment. Pre-test intra-CA1 microinjection of yohimbine [1 microg/rat] before administration of WIN55,212-2 [0.5 microg/rat, intra-CA1], however, dose-dependently inhibited WIN55.212-2 state-dependent memory. Modulation of a2-adrenergic receptors in the dorsal hippocampal CA1 regions can influence WIN55, 212-2 induced amnesia and WIN55,212-2 state-dependent learning of an inhibitory avoidance task by pre- or post-synaptic mechanism[s]

[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

[Influence of intracerebral administration of L-NAME in dorsal hippocampus [CA1] on WIN55, 212-2 induced state-dependent memory in the step-down passive avoidance test]

This study presents the effects of nitricoxide synthase inhibitor [L-NAME] on WIN55, 212-2 induced state-dependent memory of passive avoidance task, which were examined in mice. Mice were anesthetized with intra-peritoneal injection of ketamine hydrochloride, plus xylazine and then placed in a stereotaxic apparatus. Also, two stainless-steel annuals were placed 1 min above CA1. One-trial step-down paradigm was used for the assessment of memory retention in adult male NMRI mice. Post-training intra-CA1 administration of WIN55, 212-2 [0.5 and 1 micro g/mouse], dose-dependent decreased the memory retrieval. The memory impairment induced by post-training administration of WIN55, 212-2 [1 micro g/mouse], was restored by pre-test administration with the same dose of drug [1 micro g/mouse, intra-CA1]. Single intra-CA1 administration of L-NAME [0.3, 1 and 3 micro g/mouse], 5 minute pre-test could not alter memory retrieval. Also, in animals in which retrieval was impaired due to post-training administration of WIN55, 212-2 [1 micro g/mouse], pre-test intra-CA1 administration of L-NAME [0.3, 1 and 3 micro g/mouse] 24 hours after training, could not restore memory retrieval. Furthermore, in animals which received both post-training [1 micro g/mouse] and pre-test injection of WIN55, 212-2 [1 micro g/mouse], the injection of L-NAME [3 micro g/mouse, intra-CA1], 2 minute before pre-test administration decreased retrieval. These findings may demonstrate the involvement of NO in state-dependent memory induced by intra-CA1 administration of WIN55, 212-2