ABSTRACT
Background: Cholestasis is a hepatic disease, which discomposes the secretion of bile and gives rise for the aggregation of bile compounds such as bile salts, in case of non-treatment, cholestasis finds the capability to influence on different organs such as heart and brain. Besides, the disease is also quite effective on the expression rate of apoptosis and mitochondrial biogenesis genes. Thus, we went through researching about the effects of cholestasis over the changes of expressions for genes run through apoptosis [BCL-XL] in hippocampus region of male rats. We also tried for fact-finding about the impact of curcumin drug, which holds treatment impact for chronic disease such as neoplastic, inflammatory, and nervous disorders over these genes expression in rats' hippocampus
Materials and methods: The animals were divided in 4 groups of BDL, BDL- Curcumin, Sham- Curcumin, and Control. Rats of BDL group experienced BDL surgery [closing bile tubes]. Besides, of surgery, rats of BDL-Curcumin group, treated with curcumin. Animals of Sham-Curcumin just received surgery stress and treated with drug, while the animals of CONTROL just experienced surgery stress without any other interference. Then, we removed hippocampus from rats' brains and after the RNA extraction and cDNA synthesis, we investigated genes expression measurement through Real Time PCR technique
Results: Curcumin drug increased the rate of BCL-XL gene expression at the rats' hippocampus
Conclusion: The data indicated that curcumin can alter apoptosis-induced by cholestasis at the hippocampus region
ABSTRACT
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
ABSTRACT
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
ABSTRACT
Introduction: The plethora of studies indicated that there is a cross talk relationship between harmaline and serotonergic [5-HT] system on cognitive and non-cognitive behaviors. Thus, the purpose of this study is to assess the effects of hippocampal 5-HT4 receptor on memory acquisition deficit induced by harmaline
Methods: Harmaline was injected peritoneally, while 5-HT4 receptor agonist [RS67333] and antagonist [RS23597-190] were injected intra-hippocampal. A single-trial step-down passive avoidance, open field and tail flick tasks were used for measurement of memory, locomotor activity and pain responses, respectively
Results: The data revealed that pre-training injection of higher dose of harmaline [1 mg/kg], RS67333 [0.5 ng/mouse] and RS23597-190 [0.5 ng/mouse] decreased memory acquisition process in the adult mice. Moreover, concurrent pre-training administration of subthreshold dose of RS67333 [0.005 ng/mouse] or RS23597-190 [0.005 ng/mouse] with subthreshold dose of harmaline [0.5 mg/kg, i.p.] intensify impairment of memory acquisition. All above interventions did not change locomotion and tail flick behaviors
Discussion: The results demonstrated that the synergistic effect between both hippocampal 5-HT4 receptor agonist and antagonist with impairment of memory acquisition induced by harmaline, indicating a modulatory effect for hippocampal 5HT4 receptor on Harmaline induced amnesia
ABSTRACT
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.
Subject(s)
Rats , Cholestasis , Learning , Motor Activity , Bile DuctsABSTRACT
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
ABSTRACT
The plethora of studies indicated that there is a cross talk relationship between harmaline and serotonergic [5-HT] system on cognitive and non-cognitive behaviors. Thus, the purpose of this study is assessment the effects of CA1 5-HT4 receptor on memory acquisition deficit induced by harmaline. Harmaline was injected peritoneally, while 5-HT4 receptor agonist [RS67333] and antagonist [RS23597-190] were injected intra-CA1. For memory measurement,a single-trial step-down passive avoidance apparatus was used. The data revealed that pre-training injection of higher dose of harmaline [1 mg/kg], RS67333 [0.5 ng/mouse] and RS23597-190 [0.5 ng/mouse]decreased memory acquisitionprocess in the adult mice. Moreover, concurrent pre-training administration of subthreshold doseof RS67333 [0.005 ng/mouse] orRS23597-190 [0.005 ng/mouse]with subthreshold dose of harmaline [0.5 mg/kg, i.p.]intensify impairment of memory acquisition. All above interventions did not change locomotion and tail flick behaviors. In conclusion, the results demonstrated that the synergistic effect between both CA1 5-HT4 receptor agonist and antagonist with impairment of memory acquisition induced by harmaline, indicating a modulatory effect for CA1 5HT4 receptor on Harmaline induced amnesia
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Glutamatergic system stimulationthe nucleus accumbens shell, may affect anxiety-related behaviors, aversive learning and memory. Glutamate receptors are differentially distributed in pre- and postsynaptic sites contributing to neuronal communications.The present study aimed to examine the possible involvement of the NAc shell presynaptic NMDA receptors on NMDA induced responses, using the elevated-plus maze [EPM] task in maleWistar rats. Bilateral guide cannulae were implanted to allow microinjection of glutamatergic agonist [NMDA] or ca+2 channel blocker [SKF96365 hydrochloride] agents. Pretest intra-NAc shell infusion of NMDA induced anxiolytic-like behaviors and impaired the EPM-associated memory upon test and retest, respectively. In addition our findings showed that, the intra-NAc shell infusion of Ca+2 channel blocker at applied doses, does not alter the anxiety-like response and aversive memory upon test and retest, respectively. Furthermore, infusing the subthreshold dose SKF prior to the injection of effective doses of NMDA, reduced the anxiolytic-like response and improved the aversive memory impairment which had already been induced by intra-NAc shell NMDA injection. Our study showed that,inhibition of the neurotransmitter exocytosis from pre-synaptic neuron via Ca+2 channel blockade bySKF96365 decreases affected induced by NMDA in the NAc shell region, indicating the involvement of the pre-synaptic NMDA receptors in NMDA induced responses.Therefore, NMDA's ability to increase anxiolytic-like behaviors and the aversive memory impairment may be the result of an action on pre-synaptic glutamatergic receptors which in turn decrease the glutamate effect at synaptic terminal level
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Bile duct ligation [BDL] is shown to induce cholestasis-related liver function impairments as well as consequent cognitive dysfunctions [i.e. impaired learning and memory formation]. This study investigates the effects of cholestasis [14, 21 and 28 days post bile duct ligation] on spatial and non-spatial novelty detection, using a non-associative task. Male mice weighing 30-35 g were used. Cholestasis was induced by ligation of the main bile duct using two ligatures and transecting the duct at the midpoint between them. Open field paradigm was employed to assess the spatial and non-spatial memories retention. Our data showed that cholestasis [28 days after bile duct ligation] decrease and increased duration time of displace and non-displace objects respectively, indicating spatial memory deficit. Moreover, this intervention [28 days after bile duct ligation] decreased and did not alter duration time of substitute and non-substitute objects respectively, suggesting non-spatial memory deficit. Moreover, the data postulated that 14 and 21 days post bile duct ligation both spatial and non-spatial memories did not alter. Our results suggested that cholestasis [28 but not 14 and 21 days post bile duct ligation] impaired spatial and non-spatial memory in the mice
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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.
Subject(s)
Animals, Laboratory , Nucleus Accumbens , Rats, Wistar , AnxietyABSTRACT
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.
Subject(s)
Animals, Laboratory , Dopamine , Nucleus Accumbens , Glutamic Acid , Brain , Rats, WistarABSTRACT
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
Subject(s)
Animals, Laboratory , Reward , Exploratory Behavior , Analgesics, Opioid , Dopamine Agents , Mice , MorphineABSTRACT
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
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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