Effect of exercise and morphine on psychological and physical dependencies, BDNF and TrkB gene expression in rat's hippocampus

Objectives: To compare the effect of exercise and morphine on abstinence syndrome and hippocampal gene expression in rat model

Methods: Thirty adult male rats were exposed to voluntary wheel exercise [low, medium, high] for 28 days. The subjects entered Conditioned Place Preference [CPP] apparatus and experienced morphine [low, medium, high] CPP and followed by naloxone test. Correlation between exercise level, morphine injection, concurrent morphine administration and exercise with morphine CPP, BDNF and TrkB genes was determined. Rats were euthanized, decapitated and the hippocampus was removed. The expression of BDNF and TrkB genes were evaluated by real time PCR

Results: Active rats ran an average of 839.18 m/d. A significant [P<0.001] correlation between exercise level, morphine injection, concurrent morphine administration and exercise with morphine CPP and BDNF and TrKB gene expressions was found

Conclusion: Voluntary exercise in different levels potentiates the brain rewarding system, CPP scale, and hippocampal BDNF and TrKB expressions. High range of voluntary exercise demonstrated an increase in the likelihood of developing addictive and drug-seeking behavior

involvement of hippocampal CA3 TRP channels in anxiety and avoidance memory consolidation in rats tested in elevated plus maze

In the current study, we assessed the role of transient receptor potential [TRP] channels on avoidance memory and anxiety states in CA3 area of the hippocampus

We explored the anxiety and avoidance memory states using test-retest protocol in the elevated plus maze to understand whether TRP channels can affect the above mentioned states in CA3 area

To investigate the consolidation phase of memory, the drugs were injected into the CA3 region before the test

Our data showed that the application of SKF-96365 did not alter anxiety-like behaviors but induced avoidance memory impairment. It was revealed that CA3 TRP channels could affect the avoidance memory consolidation and their role must be considered in future research

Comparison of 5-HT3 or 5-HT4 agents function into the prelimbic area on passive avoidance memory consolidation

Growing evidence suggests that serotonin plays an important role in learning and memory and all its receptors might be implicated in this process. The present study aimed at investigating and comparing the possible involvement of 5-HT3 and 5-HT4 receptor [R] agonists/antagonists upon consolidation of inhibitory avoidance memory in the pre-limbic [PL] area. Bilateral intra-PL microinjections of m-CPBG [m-Chlorophenylbiguanide hydrochloride: a selective 5-HT3R agonist; 0.1 microg/rat], Y-25130 [a selective 5-HT3R antagonist; 0.1 microg/rat], RS67333 [a potent and highly selective 5-HT4R partial agonist; 0.5 microg/rat] and RS23597-190 [a selective 5-HT4R antagonist; 0.5 microg/rat] were performed immediately after training. The step-through inhibitory avoidance [IA] task was used to memory assessment in adult male Sprague-Dawley rats. Our data revealed that the post-training intra-PL microinjection of m-CPBG relative to saline and Y-25130 decreased inhibitory avoidance memory consolidation in the PL area. On the contrary, RS67333 increased IA memory consolidation in comparison to saline and RS23597-190. In addition, there was also a significant difference between the effects of m-CPBG and RS67333 on IA memory consolidation in the PL area. M-CPBG induced reduction of IA memory consolidation, while RS67333 increased it. However, Y-25130 compared to RS23597-190 did not show any significant difference. All above interventions did not alter locomotor activity. This study indicated that local direct agonist activation of 5-HT3Rs induced the reduction of IA memory consolidation, opposed to the local direct agonist activation of 5-HT4Rs, which mediated enhancement of IA memory consolidation. It can be proposed that 5-HT3Rs in comparison to 5-HT4Rs may be inversely involved in modulation of IA memory consolidation in the PL

X chromosome inactivation in opioid addicted women

Introduction: X chromosome inactivation [XCI] is a process during which one of the two X chromosomes in female human is silenced leading to equal gene expression with males who have only one X chromosome. Here we have investigated XCI ratio in females with opioid addiction to see whether XCI skewness in women could be a risk factor for opioid addiction

Methods: 30 adult females meeting DSM IV criteria for opioid addiction and 30 control females with no known history of addiction were included in the study. Digested and undigested DNA samples which were extracted from blood were analyzed after amplification of the polymorphic androgen receptor [AR] gene located on the X chromosome. XCI skewness was studied in 3 ranges: 50: 50-64: 36 [random inactivation], 65: 35-80: 20 [moderately skewed] and >80: 20 [highly skewed]

Results: XCI from informative females in control group was 63% [N=19] random, 27% [N=8] moderately skewed and 10% [N=3] highly skewed. Addicted women showed 57%, 23% and 20%, respectively. The distribution and frequency of XCI status in women with opioid addiction was not significantly different from control group [P=0.55]

Discussion: Our data did not approve our hypothesis of increased XCI skewness among women with opioid addiction or unbalanced [non-random] expression of genes associated with X chromosome in female opioid addicted subjects

Effects of Cholestasis on Learning and Locomotor Activity in Bile Duct Ligated Rats

Background: Cognitive functions are impaired in patients with liver disease. Bile duct ligation causes cholestasis that impairs liver function. This study investigated the impact of cholestasis progression on the acquisition and retention times in the passive avoidance test and on the locomotor activity of rats. Methods: Cholestasis was induced in male Wistar rats by ligating the main bile duct. Locomotor activity, learning and memory were assessed by the passive avoidance learning test at day 7, day 14, and day 21 post-bile duct ligation. The serum levels of bilirubin, alanine aminotransferase, and alkaline phosphatase were measured. Results: The results showed that acquisition time and locomotor activity were not affected at day 7 and day 14, but they were significantly (P < 0.05) impaired at day 21 post-bile duct ligation compared with the results for the control group. Additionally, memory was significantly impaired on day 7 (P < 0.01), day 14, and day 21 (P < 0.001) compared with the control groups. The levels of total bilirubin, direct bilirubin, indirect bilirubin, alanine aminotransferase, and alkaline phosphatase were significantly higher at day 7, day 14, and day 21 post-bile duct ligation compared with the levels in the sham group. Conclusion: Based on these findings, both liver and memory function were affected in the early stage of cholestasis (7 days after bile duct ligation), while learning and locomotor activity were impaired at 21 days after bile duct ligation following the progression of cholestasis.

Cyclic AMP pathway modifies memory through neural cell adhesion molecule alterations in the rat hippocampus

Neural Cell Adhesion Molecules [NCAMs] are known to influence memory by affecting neural cell-cell and cell-extracellular matrix junctions. This study investigated the possible role of cAMP pathway in the expression of hippocampal NCAM and its polysialylated derivative [PSA-NCAM]. The following pharmacological tools were employed for manipulation of cAMP pathway: a] forskolin; the activator of adenylyl cyclase [AC], b] 8-Br-cAMP; a protein kinase A [PKA] agonist, c] 8-pCPT-2'-O-Me-cAMP; a selective enhancer of exchange protein activated by cAMP [Epac] and d] Rp-cAMP; a PKA inhibitor. Memory acquisition was tested by passive avoidance paradigm after injecting the above compounds for three consecutive days into the CA1 region of dorsal hippocampus of rats. Forskolin and 8-Br-cAMP enhanced memory retrieval while Rp-cAMP significantly reduced memory and NCAM levels. 8-pCPT-2'-O-Me-cAMP failed to alter memory performance or NCAM levels as compared to vehicle. We observed no significant changes in PSA-NCAM, however the expression of St8sia4 and St8sia2 [the polysialyltransferase isoforms] were altered. The mRNA levels of St8sia4 was down-regulated by 8-Br-cAMP, Rp-cAMP and 8-pCPT while forskolin led to almost 3 and 5 fold increase in mRNAs of St8sia2 and St8sia4, respectively. The current insight might endorse the predominant role of PKA as compared to Epac in cAMP pathway in expression of NCAM and memory function

Role of 5-HT[1] receptors of accumbens shell arena upon ACPA-induced anxiolytic-like behaviors in rat

Cannabinoids induce diverse responses on anxiolytic-like behaviors. Moreover some studies postulated that there is a close relationship between this system and serotonergic system upon cognitive process formation. Thus the aim of present study is investigation the possible role of 5-HT[1] receptor on anxiolytic-like behaviors induced by ACPA in the elevated plus maze task [EPM]. In the present study rats weighting 250-300g upon surgery bilateral guide cannulae were implanted to allow microinjection of ACPA [agonist CB1 receptor], CP94253 Hcl[agonist 5-HT[1] receptor] alone and them interaction in the AcbSh. The data showed pretest AcbSh infusion of ACPA at doses of0.0002, 0.002, 0.02 and 0.2 micro g/rat increased and decreased the percentage of open-arms time [%OAT] and percentage of Enclosed-arms time [%CAT], respectively as compared to control groups. Pretest AcbSh infusion ofCP94253 Hcl at doses of 5, 0.5 and 0.05 ng/rat, did not alter anxiety-like behaviors. In addition intra-AcbSh microinjection of subthreshold dose of CP94253 Hcl did not alter ACPA-induced anxiolytic-like behaviors. Our data suggest that activation of AcbSh 5-HT[1] receptor did not involve in ACPA-induced behaviors in the EPM task

overview of cognitive aspects of beta-carbolines

Mind-altering drugs, especially plants, have fascinated human and always occupied man's attention. Among the plants used by humans, those able to alter the mind and the mood have drawn special consideration. Actually, due to their amazing effects, these drugs, have occupied much of the researchers' time and efforts towards attempts to understand their mechanism, and, hence, to understand human thoughts, behavior, cognitive aspects, sensations and etc. The fact is plants could have beneficial properties to treat mental disease and have some effects on cognitive function. Now we know that plants by originating directly from nature are not less toxic than synthetic drugs. The manner of poisoning with plants can be divided into unintentional or intentional ingestion of plant material and substance abuse. This review article deals with beta-carboline, which has effect on CNS

[Neurotrophic effect of tacrolimus on pyramidal cells of CA1 region of hippocampus following transient global ischemia/reperfusion in male wistar rat]

Cerebral ischemia is known as a major problem in the world. Reperfusion following the ischemia ultimately leads to programmed cell death or apoptosis. Specific regions of the brain and certain types of neurons are more susceptible to cerebral ischemia, such as pyramidal neurons of CA1 region of hippocampus. Recently, using of immunophilin ligands has been considered to be a potential and appropriate strategy for neuroprotective and neurogenitor activity. Up to now, the right time of injection for providing the suitable effect on pyramidal cells of CA1 has not been assessed precisely. In this study, the neurotrophic effects of tacrolimus on CA1 cells were studied on 40 male Wistar rats in 8 experimental groups. Ischemia model was induced by ligation of bilateral common carotid arteries. For detecting the most appropriate time for 6mg/kg, Injection was done via single and double doses with intervals of 6, 24, 48 and hours. The repeated doses of 6mg/kg with interval of 48 hours are the suitable dose and time of injection. It seems that tacrolimus can be an appropriate strategy as a neurotrophic drug for treating brain ischemia

time profile of morphine effect on different phases of inhibitory avoidance memory in rat

The amnesic effect of morphine is well known in the laboratory animals. But, it is unclear that morphine at what times can exactly affect different phases of memory, including acquisition, consolidation, and retrieval. Therefore, we investigated the time profile of morphine's amnesic effect on passive [inhibitory] avoidance learning and memory in male Wistar rats. In order to evaluate the outcomes of pre- and post-training administrations of morphine, the animals were trained in a step-through type of passive avoidance task at various time points, and were tested 24 h after training to measure memory retrieval. The results showed that acquisition of memory was impaired in the animals that received a dose of 7.5 mg/kg of morphine [Intraperitoneally] at 0, 30 min, and 1 h before training, as evidenced by a decrease in step-through latency on the test day. Post-training administrations of morphine at 30 min and 1h, 4h except for the time immediately after training, did not impair memory consolidation. The results also showed that pre-test administrations of morphine at 0 and 30 min before the test, impaired retrieval of inhibitory avoidance memory. Taken together, the results suggest that morphine, when injected at different time points before training, after training, or before testing affects different phases of inhibitory avoidance memory. With regard to the time of injections related to each phase, other experiments can be designed to investigate molecular mechanisms involved in the impairing effect of morphine in each phase

[ effects of nicotine injection in rat nucleus accumbens on anxiety]

Previous reports showed that nucleus accumbens involved in the etiology and pathophysiology of major depression, anxiety and addiction. It is not clear that how these mechanisms occur in the brain. In the present study, the influence of direct nicotine injection in the nucleus accumbens in rats' anxiety-related behavior was investigated. Wistar rats were used in this study. Male Wistar rats bred in an animal house, in a temperature-controlled [22 +/- 2[degree]C] room with a 12 hour light/darkcycle. Rats were anesthetized using intraperitoneal injection of ketamine hydrochloride and xylazine, then placed in an stereotactic instrument for microinjection cannula implantation The stainless steel guide cannula was implanted bilaterally in the right and left dorsal the nucleus accumbens shell according to Paxinos and Watson atlas. After recovery, anxiety behavior and locomotor activity were tested. We used the elevated plus maze to test anxiety. This apparatus has widely been employed to test parameters of anxietyrelated behaviors including the open armtime percentage [%OAT], open arm entries percentage [%OAE], locomotor activity and we record effect of drugs after injection directly in the nucleus accumbens on anxiety-related behavior. Experiments showed that bilateral injections into the nucleus accumbens Nicotine, acetylcholine receptor agonist, dose 0.1 of the dose [0.05 and 0.1, 0.25, 0.5] microgram per rat caused a significant increase in the percentage of time spent in the open arms [%OAT], compared to the control group. We did not record any significant change locomotor activity and open arm entries percentage [%OAE] in rats. Nicotinic receptors in the nucleus accumbens shell involved to anxietylike behavior in male rats.

[ possible interaction of dopamine system in nucleus accumbens shell and glutamate system of prelimbic region on locomotor activity in rat]

Nucleus accumbens [NAc] and prefrontal cortex [PFC] dopaminergic and glutamatergic systems are involved in regulating of locomotor activity behaviors. This study has investigated the interaction of NAc shell dopaminergic system and prelimbic glutamatergic systems in regulating locomotor activity and related parameters. The aim of this study was the effect the drugs injection interaction in the brain of male Wistar rats on locomotor activity and related parameters, in the order of this purpose, open field apparatus that automatically recorded locomotor activity was employed. Unilateral intra-cerebral injection of drugs was done. Unilateral intra-prelimbic injection of D-AP7 [N-methyl-D-aspartic acid=NMDA receptor antagonist; 0.25, 0.5 and 1micro g/micro l] did not alter locomotor activity behaviors. However, infusion of NMDA [0.9micro g/micro l] in this region increased locomotor activity [P<0.01], whereas decreased rearing [P<0.01] and grooming [P<0.01] which was blocked by D-AP7 [0.25micro g/micro l] [P<0.01]. Moreover, unilateral infusion of SCH23390 [dopamine D1 receptor antagonist; 0.25, 0.5 and 1micro g/micro l] into the left NAc shell did not alter locomotor activity. However, injection of SKF38393 [dopamine D1 receptor agonist; 4micro g/micro l] into the left NAc shell increased locomotor activity [P<0.05] which was blocked by SCH23390 [0.25micro g/micro l] [P<0.01]. Furthermore, the subthreshold dose infusion of SCH23390 [0.25micro g/micro l] into the left NAc shell reduced the effect of intra-prelimbic NMDA on locomotor activity [P<0.01]. In addition, intra-NAc shell administration of the subthreshold dose of SKF38393 [1micro g/micro l] potentiated the middle dose [P<0.05], whereas decreased the higher dose of intra-left prelimbic NMDA response [P<0.05] on locomotor activity. The results suggested a modulatory effect of the NAc shell dopaminergic system on increased locomotor activity by activating glutamate system in prelimbic.

effect of cholestasis on rewarding and exploratory behaviors induced by opioidergic and dopaminergic agents in mice

Several investigations have indicated that cholestasis decreases opioid receptor expression in the brain following increased opioidergic neurotransmission. The opioidergic system plays an important role in regulation of reward circuits that may be produced via dopamine-dependent mechanisms. It has been suggested that the dopaminergic system of the nucleus accumbens is necessary in conditioned place preference [CPP]. The aim of this study is, therefore, to test if cholestasis can alter the reward system and the involvement of opioidergic and dopaminergic systems in this phenomenon. We used CPP and hole-board paradigms to measure the reward effect and exploratory behaviors, respectively, in mice. Cholestasis was induced by ligation of the main bile duct, using two ligatures and transecting the duct between them [BDL mice]. The data showed that morphine [1 and 2 mg/kg], sulpiride [80 mg/kg] and SKF38393 [20 mg/kg] produced CPP, while naloxone [1 mg/kg] and SCH23390 [1 mg/kg] produced conditioned place aversion [CPA], whereas quinpirole had no effect in sham-operated mice. However, morphine [2 mg/kg, i.p.], sulpiride [40 mg/kg] and SKF38393 [10 mg/kg] induced CPP in BDL mice compared to sham-operated mice. Naloxone- or SCH23390-induced CPA was reduced in BDL mice compared with the respective sham-operated mice. Quinpirole tended to induce aversion in BDL mice which was, however, not significant. In addition, quinpirole 1 mg/kg] and SCH23390 [1 mg/kg] increased head-dip exploratory behavior, whereas naloxone [2 mg/kg] caused a decrease in head-dip exploratory behavior in sham-operated mice. Morphine [2 mg/kg], SCH23390 [1 mg/kg] and quinpirole [0.25 and 0.5 mg/kg] induced anxiogenic-like behavior in BDL mice. It can be concluded that cholestasis differentially alters the reward effects of opioidergic and dopaminergic agents

Acute administration of Zn, Mg, and thiamine improves postpartum depression conditions in mice

Background: Postpartum depression [PPD] affects approximately half of new mothers. Chronic exposure to progesterone during pregnancy and its withdrawal following delivery increases depression and anxiety. In addition, there are complex interactions between hormones, neurotransmitters, and trace elements. Zinc [Zn] and magnesium [Mg] in Auence the nervous system by impacting synaptic neurotransmis-sion in the brain. Thiamine [Vit B[1]] deficiency results in a high percentage of depressive behaviors. Elevated levels of reactive oxygen species in pregnancy are implicated in the pathogenesis of major depression

Methods: We examined the effects of different combinations of Zn, Mg, and Vit B[1] in an animal model of PPD. ZnCl, MgCl, and thiamine-HCl were administered to PPD-induced mice. Depression, anxiety-related behavior, and total antioxidant capacity [TAC] were assessed. Depression and anxiety-like behavior were evaluated by the forced swimming test [FST] and elevated plus-maze, respectively

Results: The acute combined administration of Zn, Mg, and Vit B[1] significantly decreased immobility time in FST, increased the percentage of both time spent in-and entries to open arms in the elevated plus-maze, and augmented TAC

Conclusion: Our data suggest that acute administration of combined treatment with Zn, Mg, and Vit B[1] on postpartum day 3 improves depressive symptoms and anxiety-like behaviors. Our evaluation of TAC is in accordance with behavioral results

Morphine-induced nitric oxide production in PC12 cells

The role of nitric oxide [NO] in many well-known effects of morphine is well defined. NO is involved in the signaling pathway of the N-methyl-D-aspartate [NMDA] receptor, which is proposed to mediate some of morphine's effects. This research studies the effect of morphine and NMDA on lipopolysaccharide [LPS]-stimulated NO production by clonal rat pheochromocytoma [PC12] cells. We used the Griess reaction to measure NO concentrations in cell culture medium. PC12 cells that were incubated for 24 h with varying concentrations of morphine [0.1, 1, 10, 100, and 1000microM] plus LPS [1 microg/ml] did not significantly alter the concentration of NO in the medium. However, NO production increased when cells were treated for both 48 h with 100 and 1000 microM morphine and for 72 h with 10,100, and 1000 microM of morphine. After 72 h, 1 microM naloxone significantly decreased NO concentration. Naloxone, at doses of 0.1, 1, and 10microM prevented NO production by 1000 microM of morphine. NMDA [0.1, 1, and 10 microM] did not alter NO concentrations after 24, 48 or 72 h. Morphine [1 microM]-induced NO production was inhibited by 10 microM NMDA after 48 h. Inhibition of NO was also noted with1 and 10 microM concentrations of morphine after 72 h. Chronic treatment of PC12 cells with morphine significantly increases LPS-stimulated NO production via naloxone-sensitive receptors. The cells seem to release endogenous morphine in medium. NMDA does not affect NO production, which may be due to the lack of functional NMDA receptor expression in PC12 cells

Involvement of nitric oxide system on anxiolytic-like behaviors induced by cholestasiss

The mechanisms of hepatic encephalopathy are not fully understood. Moreover, there is no comprehensive data concerning the effects of nitric oxide [NO] system on anxiolytic-like behaviors induced by bile duct ligation [BDL]. Male mice weighing 25-30 g were used and anxiety-like behaviors were tested using hole-board task. The data indicated that cholestasis increased the number of head-dipping but did not alter other aspects of behavior, 7 days after BDL, suggesting an anxiolytic-like response. Furthermore, the results showed that intraperitoneal [i.p.] injection of L-arginine [200 and 250 mg/kg] 15 min before testing induced anxiolytic-like behaviors in the normal animals, 4 and 7 days after BDL [considering that the dose of 200 mg in the normal mice is ineffective but is effective in the BDL mice]. On the other hand, injection of L-NAME [35 and 45 mg/kg, i.p.] 15 min before testing induced anxiogenic-like behaviors in the normal animals, 4 and 7 days after BDL [the dose of 35 mg/kg in the normal mice is ineffective but is effective in the BDL mice]. Moreover, injection of ineffective doses of L-NAME [25 and 35 mg/kg, i.p.] 15 min before administration of L-arginine [250 mg/kg, i.p.] and 7 days after BDL, decreased anxiolytic-like behaviors, significantly. Cholestatic mice show anxiolytic-like behaviors suggesting the involvement of the nitric oxide system

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

Repeated pretreatment of morphine prevents morphine-induced amnesia: a possible involvement for dorsal hippocampal NMDA receptors

Background: learning and memory processes can be affected by morphine administration. It has been previously demonstrated that the effects of morphine depend on the timing of drug administration. In the present study, the effects of microinjections of a NMDA receptor agonist and antagonist into the CA1 regions of the dorsal hippocampi [intra CA1] on repeated pretreatment of morphine-induced prevention of morphine-induced amnesia have been investigated

Methods: step-through inhibitory avoidance task of memory has been used to examine retrieval of memory formation, 24 h after training in male Wistar rats

Results: the results indicate that post-training administration of morphine [7.5 mg/kg] impaired memory retrieval, but not in the animals, which received previous repeated morphine [7.5 and 10 mg/kg] injections followed by morphine withdrawal. Repeated co-administration of NMDA [7.5 and 10 ng/rat, intra-CA1] with an ineffective dose of morphine [5 mg/kg], once daily for three days reversed morphine-induced amnesia. Repeated bilateral intra-CA1 microinjections of NMDA, once daily for three days followed by a five-day washout had no effect on the expression of amnesia produced by post-training morphine. Three-day administration of the NMDA receptor antagonist, D-AP5 [0.5 - 2 micro g/rat, intra-CA1] followed by a five-day washout had no effect on morphine-induced amnesia. On the other hand, intra-CA1 microinjections of the same doses of D-AP5 prior to injection of 7.5 mg/kg of morphine [per day×3 days] decreased the reversal of morphine-induced amnesia

Conclusion: these data imply that the dorsal hippocampal NMDA receptor mechanism[s] may modulate the effect-induced by repeated morphine administration on a challenge dose of morphine-induced amnesia

[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