maryam sadat shahin

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.

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. 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.

Nitric oxide synthase enzyme has been detected in the Nucleus accumbens، which is the targetareas of the mesolimbic dopamine pathways. In the present study، the effect of intra-NAc administration of the nitric oxide precursor was investigated on nicotine’s effects in ethanol state-dependent learning. Rats were anesthetized with intra-peritoneal injection of ketamine hydrochloride، plus xylazine and two stainless-steel cannuale were placed 2 mm above nucleus accumbens of them. One week later، the animals were trained in a step-through type inhibitory avoidance task. On the test day step-through latency was measured for the assessment of memory in male Wistar rats. Pre-training injection of ethanol induced amnesia (P<0. 001). The amnesia induced by pre-training ethanol restores with pre-test administration of same dose of ethanol (P<0. 001). This phenomenon، referred to as ethanol state-dependent learning. Pre-test injection of nicotine by itself had no effect on inhibitory avoidance memory (P>0. 05). However، restored amnesia was induced by ethanol (P<0. 001). In contrast، pre-test intra-NAc injection of L-arginine which had no effect alone (P>0. 05) prevented the nicotine reversal effect on ethanol memory impairment (P<0. 001). Our data indicated that nitric oxide precursor can inhibit the improving effect of nicotine on the ethanol-induced amnesia.

Nitric oxide and mecamylamine have an important role in anxiety-like behavior. Determining the site of action in the brain and interaction between these agents need to be investigated. Therefore، this study aimed to investigate the possible interaction between mecamylamine and nitric oxide in dorsal hippocampus using the elevated plus-maze test of anxiety. This experimental study was performed on 180 male NMRI mice. Mice were anaesthetized with ketamine and xylazine and two cannuale were inserted stereotaxically into the CA1 region of the dorsal hippocampus. All animals were allowed to recover for 1 week before the beginning of the behavioral testing. The elevated plus-maze was used to test the anxiety-like behavior. Bilateral intra-dorsal hippocampal injections of mecamylamine، L-arginine or L-NAME induced the anxiogenic effects. Intra-dorsal hippocampal injection of ineffective dose of mecamylamine before different doses of L-arginine or L-NAME potentiated the anxiogenic effects of L-arginine or L-NAME. Results reveal that both nitric oxide and mecamylamine not only play a part in the modulation of anxiety in the dorsal hippocampus of mouse but also have demonstrated a complex interaction as well.

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 µg/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 L-arginine 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.

β-carbolines alkaloids suchv 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 µg/mice) also induced amnesia. On the other hand, pre-test intra-CA1 injection of ineffective doses of mecamylamine (0.5, 1 and 2 µg/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.

Histaminergic and dopaminergic systems influence anxiety-related behavior. Furthermore, interaction between histaminergic and dopaminergic receptors has been demonstrated in the modulation of some behaviors in the hippocampus. In the present study, the interaction between histaminergic and dopaminergic receptors of dorsal hippocampus in the anxiety-related behavior has been evaluated. This experimental study was carried out on 140 male NMRI mice. Mice were anesthetized with intra-peritoneal injection of ketamine hydrochloride plus xylazine and then placed in a stereotaxic apparatus. Two cannuales were placed in the CA1 region of hippocampus. All animals were allowed to recover for one week before the beginning of the behavioral testing. The elevated plus-maze test was used to evaluate anxiety-related behaviors. One-way analysis of variance (ANOVA) followed by LSD test were done for the statistical analysis of the data. All experiments were conducted in accordance with institutional guidelines for animal care and use. Intra-CA1 injection of histamine (10 µg/mouse) or apomorphine (0.1 and 0.3 µg/mouse) 5 min before testing induced anxiety. Intra-CA1 injection of apomorphine (0.01 and 0.1 µg/mouse) 2 min before the effective dose of histamine (10 µg/mouse) inhibited the anxiogenic effects of histamine. It seems that both histaminergic and dopaminergic system not only play a role in the modulation of anxiety in the dorsal hippocampus of mice but also demonstrate a complex interaction as well.

In this study the effects of dopaminergic D1 receptor of dorsal hippocampuson anxiety-like behavior induced by stimulation or inhibition of NMDA receptors wereinvestigated in male Wistar rats. The elevated plus maze was used in thepresent study, which is an accepted model to examine anxiety-like behaviors in mice andrats. The results indicate that intra-CA1injection of MK801 (2 μg/rat) induceanxiolytic effects. Intra-CA1 injection of SCH23390 (0.25, 0.5 and 1 μg/rat) by itselfhas no effect on anxiety-like behaviors, but administration of same doses of SCH23390before MK801 (1 μg/rat, intra-CA1) potentiate anxiolytic effects of MK801. On the otherhand, intra-CA1 injection of NMDA (0.3 and 0.6 μg/rat) or SKF 38393 (3 and 6 μg/rat) byitself induces anxiogenic effects. Injection of different doses of SKF38393 before NMDApotentiated anxiogenic effects of NMDA. These results show that bothNMDA receptor and dopaminergic D1 receptor not only play a part in the modulationof anxiety in the dorsal hippocampus of rats but also have demonstrated a complexinteraction as well.

β-carbolines alkaloids such as Harmane have been found in common plant-derived foodstuffs such as 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 nitric oxide agonist and antagonist on amnesia induced by Harmane was examined in mice. In this experimental study 305 adult male NMRI mice were used. Mice were anaesthetized and cannulae implanted bilaterally in the CA1 regions of the dorsal hippocampus using stereotaxic method. One week after cannulae implantation, mice trained in a step-down type inhibitory avoidance task, and tested 24 h after training to measure step-down latency as a scale of memory. Pre-training systemic injection of Harmane induced amnesia. Pre-test intra-dorsal hippocampal injection of L-arginine (8 µg/mouse) or L-NAME (10 and 15 µg/mouse) potentiate and reverse amnesia induced by pre-training Harmane, respectively, but pretraining injection of L-arginine or L-NAME 5 min before Harmane could not block Harmane amnesia. The finding in this study indicated that exist complex interaction between nitric oxide system of dorsal hippocampus and amnesia induced by Harmane.

Drugs of abuse such as nicotine and morphine used systemically by addicts produce their effects via the mesolimbic dopaminergic pathway. Furthermore, evidence indicates that some behavioral effects of nicotine and morphine are mediated by nitric oxide (NO). Based on these observations, the aim of the present study was to investigate the effects of intra-nucleus accumbens (NAc) injection of a nitric oxide synthase (NOS) inhibitor, L-NAME, on the nicotine’s effect on the morphine-induced amnesia. As a model of memory assessment, a step-through type passive avoidance task was used. All animals were bilaterally implanted with a chronic cannulae in the NAc shell and trained by using a 1 mA foot shock. Animals were tested 24 h after training to measure step-through latency. Post-training injection of morphine impaired memory performance on the test day. Pre-test administration of the same doses of morphine reversed amnesia induced by post-training administration of morphine. Moreover, administration of nicotine before the test prevented morphine amnesia. Impairment of memory because of post-training injection of morphine was also prevented by pretest administration of L-NAME. Co-administration of an ineffective dose of nicotine with ineffective doses of L-NAME synergistically improved memory that was impaired by morphine. On the other hand, pre-test intra-NAc injection of L-NAME impaired passive avoidance memory by itself. Considering the effects of pre-test intra-NAc injection of L-NAME alone or in combination with ineffective dose of nicotine on morphine amnesia, it may be concluded that nitric oxide system of nucleus accumbens has an important role in the improvement of morphine-induced amnesia and morphine state-dependent memory caused by nicotine.

Cannabinoids are a class of psychoactive compound that produce a wide array of effects in a large number of species. In the present study، the effects of cannabinoidergic systems and H1 receptor agents on anxiety-related behaviors and their interactions were investigated، using hole-board test in mice. Bilateral intra-CA1 administration of CB1/CB2 receptor agonist، WIN55، 212-2 (0. 1- 0. 5μg/mice) did not modify exploratory behaviors in mice. On the other hand، intra-CA1 administration of CB1 receptor antagonist، AM251 (25 and 50 ng/mice) or histamine، pyrilamine (5- 10μg/mice) decreased the number of head-dipping and increased the first head-dip، suggesting anxiogenic-like response. Furthermore، our present data indicated that co-administration of WIN55، 212-2 (0. 25μg/mice) with histaminergic agents، decreased the anxiogenic-like response of an effective dose (5μg/mice) of histamine and pyrilamine. In addition، the results demonstrated that co-administration of an ineffective dose of AM251 (25 ng/mice) with histaminergic drugs did not alter the response induced by an ineffective dose (2. 5μg/mice) of either histamine or pyrilamine. In all experiments in doses used، locomotor activity was not significantly changed. Our results showed that there may be a partial interaction between the cannabinoidergic and the histaminergic systems of the dorsal hippocampus on anxiogenic/anxiolytic-like behaviors in hole-board test.

β-carboline alkaloids, such as harmane, are found in common plant-derived foodstuffs and plant-derived inhalation components of tobacco. In the present study, the involvement of dorsal hippocampus nicotinic receptor in the harmane effects on anxiety behavior has been evaluated. Mice were anesthetized with an intra-peritoneal injection of ketamine hydrochloride plus xylazine and then placed in a stereotaxic apparatus. Cannual were bilaterally implanted in the CA1 region of hippocampus. All animals were allowed to recover for 1 week before the beginning of the behavioral testing. The hole-board test was used to evaluate the anxiety-like behaviors. One-way analys was of variance so that Dunnett’s test was used to analyse data. All experiments were performed in accordance with institutional guidelines for animal care and use. Intraperitoneal injection of harmane decreased the number of head dip and locomotion (P<0.001). While bilateral intra-dorsal hippocampal injections of nicotine decreased the number of head dip (P<0.01), it had no effect on locomotor activity. Furthermore, intra-dorsal hippocampal injection of mecamylamine (nicotinic receptor antagonist) in the presence and absence of harmane had no effect on anxiety behavior and locomotion (P>0.05). harmane and nicotine not only display anxiogenic effects but also demonstrate a complex interaction. The findings also indicated that harmane induces anxiety via non-nicotinic receptors.

Excitatory transmission through glutamate receptors is critical for cognition such as learning and anxiety. In the present study, the involvement of dorsal hippocampal muscarinic cholinergic receptor on anxiety-like behavior induced by inhibition of NMDA receptors was investigated. In this experimental study, 105 adult male rats weighing 200–250 g were used. The animals were anaesthetized and cannulae implanted bilaterally in the CA1 regions of the dorsal hippocampus using stereotaxic device. Seven days after recovery from surgery, the behavioral testing was started in elevated plus maze task. The data were analyzed using one-way analysis of variance (ANOVA) followed by Tukey test. Our finding indicated that intra-CA1 administration of MK801 (2 μg/rat) and scopolamine (4 μg/rat) by itself increased percentage of open arm time and open arm entries but did not alter locomotion. On the other hand, intra- CA1 co-administration of ineffective doses of scopolamine with ineffective dose of MK801 (1 μg/rat) did not alter locomotion activity but increased percentage of open arm time and open arm entries. These results show that both NMDA receptors and muscariniccholinergic receptors not only play a part in the modulation of anxiety in the dorsal hippocampus of rats but also demonstrate a complex interaction as well.