[ effect of L-arginine in the ventral tegmenta area on the improving effect of nicotine on memory]

Nitric oxide synthesis has been detected in ventral tegmental area, which is a key brain region that seems to mediate behavioral effect of morphine and nicotine. In the present study, the effects of L-arginine, a nitric oxide precursor, in the ventral tegmental area in nicotine's effect on morphine-induced amnesia has been investigated. This study was done experimentally on 250 male rats. Rats were anesthetized with intra-peritoneal injection of ketamine hydrochloride, plus xylazine and then placed in a stereotaxic apparatus. Two stainless-steel cannuale were placed in the ventral tegmental area. The behavioral testing was started in inhibitory avoidance task, and the step-through latency for entering into the dark compartment was measured for the assessment of memory retention. One-side analysis of variance [ANOVA] and Tukey test were used to evaluate the statistical significance between experimental groups. A difference of p<0.05 was considered statistically significant. Post-training injection of morphine [5 and 7.5mg/kg] decreased the memory retrieval. Injection of nicotine or L-arginine before test by itself has no effect on memory retrieval. On the other hand, pre-test administration of morphine [7.5mg/kg], nicotine [0.5 and 1mg/kg], L-arginine or ineffective doses of L-arginine plus non-effective dose of nicotine restored memory impairment induced by post-training injection of morphine. The finding of the study indicate that nitric oxide system of the ventral tegmental area may play an important role in the improving effect of nicotine on the morphine-induced amnesia

[Interaction between apomorphine and histaminergic system of mouse dorsal hippocampus in the elevated plus-maze test of anxiety]

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 alpha g/mouse] or apomorphine [0.1 and 0.3 alpha g/mouse] 5 min before testing induced anxiety. Intra-CA1 injection of apomorphine [0.01 and 0.1 alpha g/mouse] 2 min before the effective dose of histamine [10 alpha g/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

[Interaction between cannabinoidergic system and H2 receptors in CA1 region upon anxiety-like behaviors in Hole-Board test]

Cannabinoids produce a wide array of effects on different species and interact with different neurotransmitter systems in the brain. In the present study, the effects of histaminergic and cannabinoidregic systems as well as their interactions on anxiety-related behaviors were examined on mice. In this study, at first mice were anesthetized with intra-peritoneal injection of ketamine hydrochloride and xylazine. They were then placed in a stereotaxic apparatus. Two stainless-steel cannuale were placed one mm above CA1 regions of the dorsal hippocampus. After that, seventeen groups of animals were tested with hole board apparatus for measuring anxiety behavior. For the statistical analysis, One-way analysis of variance [ANOVA] and Dunnett's test were used. Intra-CA1 injection of WIN55, 212-2 [0.1, 0.5 microg/mice] did not modify anxiety-related behaviors in mice. But administration of AM251 [25 and 50ng/mice], histamine or ranitidine [5micro g/mice] induced anxiogenic-like response. Also, co-administration of WIN55, 212-2 with histaminergic agents, decreased the anxiogenic-like response of histamine, but not that of ranitidine. Co-administration of an ineffective dose of AM251 with histaminergic drugs did not alter the response induced by these drugs. In all the experiments, locomotor activity was not significantly changed. These results showed that there may be a partial interaction between the cannabinoidergic and the histaminergic systems of the dorsal hippocampus on anxiety-like behaviors

[Interaction between dopamine D2 and NMDA receptors in the dorsal hippocampus of rats in the elevated plus-maze test of anxiety]

Different studies have indicated that glutamate and dopamine are involved in producing anxiety. Furthermore, interaction between NMDA and dopamine receptors has been demonstrated in the modulation of some behaviors. In the present study, the role of dopaminergic D2 receptor in producing anxiety-like behavior induced by inhibition of NMDA receptors was investigated in male wistar rats. Rats were anesthetized with intra-peritoneal injection of ketamine hydrochloride, plus xylazine and then placed in a stereotaxic apparatus. Two stainless-steel cannuale were placed in the CA1 region of hippocampus. All animals were allowed to recover for one week before beginning behavioral test. The elevated plus maze test was used to test anxiety-like behaviors. The results of this study showed that intra-CA1 injection of MK801 [2 micro g/rat] induced anxiolytic effects. Intra-CA1 injection sulpiride [0.25, 0.5 and 0.75 micro g/rat] by itself had no effect on anxiety-like behaviors, but administration of the same doses of sulpiride 5 mins before injection of the effective dose of MK801 [2 micro g/rat, intra-CA1] inhibited anxiolytic effects of MK801. The results indicated that CA1 region of hippocampus have an important role in anxiolytic effects of MK801; and anxiolytic effect of NMDA receptors antagonist is at least partly mediated via D2 receptors of the dorsal hippocampus

[Influence of intracerebral administration of l-arginine in dorsal hippocampus [CA1] on win55, 212-2 induced state-dependent memory]

Cannabinoids are a class of psychoactive compounds that produce a wide array of effects in a large number of species. In the present study, the effects of bilateral intra-CA1 injections of L-arginine on WIN55, 212-2 induced state-dependent memory of passive avoidance task was examined in mice. One-trial step-down paradigm was used for the assessment of memory retention in adult male NMRI mice. Post-training intraCA1 administration of cannabinoid receptor agonist, WIN55, 212-2 [0.5 and 1 micro g/mouse], decreased the memory retrieval. The memory impairment induced by post-training administration of WIN55, 212-2 [1micro g/mouse]was restored by pre-test administration of the same dose of the drug, showing the state-dependent memory of WIN55, 212-2. Single intra-CA1 administration of L-arginine [0.3, 1 and 3 micro g/mouse] 5min pre-test could not alter the memory retrieval. On the other hand, in the animals in which retrieval was impaired due to post-training administration of WIN55, 212-2 [1micro g/ mouse], pre-test intra-CA1 administration of L-arginine [1 and 3 micro g/ mouse], 24hr after training restored memory retrieval. Furthermore, in the animals under influence of post-training administration of WIN55, 212-2 [1 micro g/mouse], pre-test co-administration of non-effective doses of WIN55, 212-2 and L-arginine, increased the restoration of memory by the pre-test WIN55, 212-2. The findings of the present study suggest that NO system of dorsal hippocampus may play an important role in WIN55,212-2-induced amnesia and WIN55,212-2 state-dependent memory

[Interaction between harmane and nicotinic in the passive avoidance test]

A number of beta-carboline alkaloids such as harmane are naturally present in the human food chain. Furthermore, some plants which contain beta-carboline have behavioral effects such as hallucination. In the present study, the effect of intra-dorsal hippocampus injection of nicotinic receptor agonist on memory impairment induced by harmane was examined in mice. This study was conducted at Shahid Beheshti University in 2009. Two hundred and forty mice were anesthetized with intra-peritoneal injection of ketamine hydrochloride, plus xylazine which afterwards were placed in a stereotaxic apparatus. Two cannuale were placed in the CA1 regions of the dorsal hippocampus. All animals were allowed to recover for a total week before beginning of the behavioral testing. After that, the animals were trained in a step-down type inhibitory avoidance task and tested 24 hours after training to measure step-down latency as a scale of memory. Pre-training and post-training, intra-peritoneal injection of harmane impairs inhibitory avoidance memory, but pre-testing injection of harmane did not alter memory retrieval. Pre-testing administration of high dose of nicotine [0.5 micro g/mice, intra-CA1] decreased memory retrieval. On the other hand, pre-test intra-CA1 injection of ineffective doses of nicotine [0.1 and 2.5 micro g/mice] fully reversed harmane induced impairment of memory. The present results indicated that complex interaction exists between nicotinic receptor of dorsal hippocampus and the impairment of inhibitory avoidance memory induced by harmane

[ effect of dorsal hippocampal alpha2-adrenegic receptors on WIN55,212-2 state-dependent memory of passive avoidance]

Cannabinoids are a class of psychoactive compounds that produce a wide array of effects in a large number of species. In the present study, the effects of bilateral intra-CA1 injections of an alpha2-adrenergic receptor agents, on WIN55, 212-2 state-dependent learning were examined in adult male Wistar rats. The animals were bilaterally implanted with chronic cannulae in the CA1 regions of the dorsal hippocampus, trained in a step-down type inhibitory avoidance task, and tested 24h after training to measure step-down latency. Post-training intra-CA1 injection of WIN55, 212-2 [0.25 and 0.5microg/rat] induced impairment of memory retention. Amnesia produced by post-training WIN55, 212-2 [0.5microg/rat] was reversed by pre-test administration of the same dose of WIN55, 212-2 that is due to a state-dependent effect. Pre-test intra-CA1 injection of clonidine [0.5 and 0.75microg/rat, intra-CA1] improved post-training WIN55, 212-2 [0.5microg/rat, intra-CA1]-induced retrieval impairment, while pre-test intra-CA1 injection of yohimbine [1microg/rat, intra-CA1] 2min before the administration of WIN55, 212-2 [0.5microg/rat, intra-CA1] inhibited WIN55, 212-2 state-dependent memory. These results suggest that alpha2-adrenergic receptors of the dorsal hippocampal CA1 regions may play an important role in Win55, 212-2-induced amnesia and WIN55, 212-2 state-dependent memory

[ interaction between harmane and nicotinic receptors of dorsalhippocampus in a hole-board test of anxiety in mice]

beta-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 nonnicotinic receptors

[Mechanism of the interaction of cannabinoid system in central amygdale with opioid system]

Cannabinoids which are active compounds of marijuana show some pharmacological effects similar to the opioids. There are also functional interactions between both cannabinoid and opioid systems. In this study we investigated the role of cannabinoid receptors in central amygdala and its interaction with opioid system. In the present study, we investigated the effects of intraperitoneal injection of opioid drugs on response-induced by intra-amygdala [intra-Amyg] microinjection of cannabinoid agents in rats, using elevated plus-maze test of anxiety. Intraperitoneal injection of morphine [3, 6 and 9 mg/kg] increased%OAT and%OAE, but not locomotor activity, showing an anxiolytic response. However, some doses of the opioid receptor antagonist, naloxone reduced%OAT and locomotor activity as well. Intra-Amyg administration of CB1 cannabinoid receptor agonist, ACPA [at the dose of 1.25 and 5 ng/rat] increased%OAT and%OAE but not locomotor activity, thus showing an anxiolytic response, which was increased by morphine [6 mg/kg, i.p.] without any interaction. Naloxone also reduced ACPA effects. Intra-Amyg administration of CB1 cannabinoid receptor antagonist, AM251 [2.5, 25 and 100 ng/rat] did not alter%OAT and%OAE but higher doses of drug [25 and 100 ng/rat] reduced locomotor activity. However, the drug in combination of morphine anxiolytic response and with naloxone decreased anxiety. The results may indicate an anxiolytic for CB1 cannabinoid. Our results also showed that opioid system may have interaction with cannabinoid receptor in the amygdale

[ effects of intra-locus coeruleus injection of dopamine D2 receptor agents on Naloxone withdrawal signs in Morphine-dependent rats]

Opiate-induced addiction is a main social problem in Iran. As treatment of this problem is a health priority among the medical community, studies on this topic are very crucial. The exact mechanism of dependence on opiates and their withdrawal syndrome remain unclear. It seems that dopaminergic system and locus coeruleus [LC] have an important role in the expression of somatic signs during opioids withdrawal. The LC has been shown to contain significant levels of dopamine [DA]. In the present study, the effects of different D2 dopaminergic receptor agonist and antagonist administration in the LC on withdrawal sign expression in morphine dependence is investigated in rats. Adult male Wistar rats, weighing 220-280 g were divided into eight groups [n=8]. Two cannulae were stereotaxically implanted bilaterally into the LC of each rat. After a one-week recovery, seven groups were rendered dependent on morphine by subcutaneous injection during a seven-day period. Non-dependent control animals received saline according to the same protocol. Animals received bilateral intra-LC injections of saline [1 micro g/site] and quinpirole [0.1, 0.3 and 0.5 micro g/site, a D2 agonist] 15 min and sulpiride [5, 15 and 30 micro g/site, a D2 antagonist] 30 min prior to naloxone injection about 24 hours after the last dose of morphine or saline according to their respective group. To calculate the total withdrawal score, as an index of withdrawal syndrome, 20 different withdrawal signs were assessed and the scores of the intensity of these withdrawal signs were added. Total withdrawal scores were significantly decreased by quinpirole [0.1micro g/site] and sulpiride [15 and 30 micro g/site]. The D2 dopaminergic system in the LC may be involved in the morphine-induced dependency in rats. Further studies are needed to define the mechanism of this dependency in order to improve methods for the rehabilitation of addicts

Analgesic effect of codeine plus bromocriptine during simple teeth extraction and minor oral soft tissue surgery

Objective-In this study, the effect of codeine alone and in combination with D2 dopamine agonist bromocriptine in pain sensation during simple tooth extraction or minor oral soft tissue surgery has been examined. Method-Patients [121 male and 91 female] who were undergoing one of the above procedures, were included in this double-blind study. They were given randomly one of the following medications: Codeine [10-20 mg], bromocriptine [2.5-5 mg] in different combinations controlled by a placebo and a dental lidocaine cartridge group. The medication was given 20 minutes before the procedure and the patients subsequently recorded their pain intensity on a scale of 0-3. Results-ANOVA showed significant difference between placebo group and cases who received the combination of bromocriptine and codeine [with certain dosages], but the analgesic effect was significantly lower than the lidocaine group [p<0.05]. Discussion-Patients who received bromocriptine 5 mg plus codeine [10 or 20 mg] had a better effective response than those receiving either of the components alone or placebo. It appears that D2 activation potentiates the response induced by the opioid agonist codeine

Morphine and Apomorphine Inhibit Gastrointestinal Transit [GIT] Through Two Different Mechanisms

Morphine was used as a remedy for the control of diarrhea centuries before it's sedative-analgesic effect was discovered. Although several mechanisms have been proposed for the morphine-induced inhibition of gastrointestinal transit [GIT], the exact mechanism has not yet been identified. On this basis the possible involvement of the dopaminergic system in morphine-induced inhibition of transit was investigated. This study showed that morphine decreased gastrointestinal transit [GIT] of charcoal dust in mice in a dose-dependent manner. The response was inhibited by the opiate antagonist naloxone. Pretreatment of animals with the D-2 antagonist sulpiride or the peripheral dopamine antagonist domperidone did not alter the morphine-induced inhibition of GIT. The D-l/D-2 agonist apomorphine also decreased GIT in mice. The response was inhibited by SCH 23390 or sulpiride pretreatment [p<0.01], but not by domperidone or naloxone. It is concluded that morphine and apomorphine inhibit GIT through opiate and dopaminergic mechanisms, respectively

Involvement of supraspinal alpha-adrenergic receptors in tonic pain

The involvement of supraspinal alpha-adrenergic receptors in tonic pain was assessed in formalin-induced pain in rats. The alpha [2] adrenoceptor agonist clonidine, along with yohimbine and prazosin, Alpha2 and Alpha1 receptor antagonists, were introduced intracerebroventrically [icv] and/or systemically in different doses. The data show that 1] clonidine exerts an alpha adrenergic analgesic effect, in addition to its known alpha [2] role in this kind of pain, 2] icv yohimbine did not change the rat's nociception, and 3] icv prazocin also failed to alleviate the animal's nociception although both the latter drugs show analgesic activity in the formalin test when injected systemically. It can be concluded that Alpha1 receptors contribute significantly to adrenergic analgesia in the formalin test in supraspinal structures, by undefined nature and site[s]