Mohammad Reza Zarrindast

Institute for Research in Fundamental Sciences (IPM), Teheran, Tehrān, Iran

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Publications (261)515.37 Total impact

  • Shahram Zarrabian · Maryam Farahi · Mohammad Nasehi · M.-R. Zarrindast
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    ABSTRACT: Cognitive functions are influenced by memory and anxiety states. However, a non-linear relation has been shown between these two domains. The important role of the hippocampus in memory and emotional responses may link the pathogenesis of anxiety to memory-related GABAergic and glutamatergic processes in the hippocampus. To investigate the role of GABAA receptors in relation to blocking N-methyl-D-aspartate (NMDA) receptors in the CA3 region, and balancing the glutamatergic and GABAergic system activities as an approach for the management of related disorders, the elevated plus-maze test-retest paradigm was used to investigate the anxiolytic-like state on the test day and avoidance memory state on the retest day. The data showed that injection of D-AP5, the NMDA receptor antagonist, induced anxiolytic-like behavior and impaired avoidance memory. Injection of GABAA agonist (muscimol), but not the antagonist (bicuculline), induced avoidance memory impairment. Neither muscimol nor bicuculline altered anxiety-like behaviors. Muscimol pretreatment did not change D-AP5-induced anxiolytic-like behaviors but potentiated avoidance memory impairment. Bicuculline pretreatment blocked D-AP5-induced anxiolytic-like behaviors and contradicted its effect on avoidance memory. Our findings indicate that alteration of the CA3 GABAA receptor activity can effectively affect the anxiolytic-like behaviors and avoidance memory deficit induced by D-AP5.
    No preview · Article · Jan 2016 · Journal of Psychopharmacology
  • Sakineh Alijanpour · Fatemeh Tirgar · M.-R. Zarrindast
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    ABSTRACT: The present study was examined the blockade of CA1 orexin-1 receptors (OX1Rs) of dorsal hippocampus in the induction or expression phase on morphine sensitization-induced memory restoration using Morris water maze (MWM) apparatus. Results showed that pre-training administration of morphine (5 mg/kg, s.c.) increases escape latency and traveled distance, while does not alter swimming speed. This supports the impairing effect of morphine on the spatial memory acquisition in male adult rats. Also, in retrieval session (probe trial) this treatment decreased the spent time and the traveled distance in the target quadrant. Moreover, morphine-induced sensitization (15 or 20 mg/kg; s.c., once daily for 3 days and followed by 5 days no drug treatment) restored the memory acquisition/retrieval deficit which had been induced by pre-training administration of morphine (5 mg/kg, s.c.). Intra-CA1 microinjection of subthreshold doses of SB-334867 (OX1Rs antagonist; 10, 20 and 40 nmol/rat), 5 min before morphine (20 mg/kg/day×3 days, s.c.; induction phase for morphine sensitization) did not alter restoration of memory acquisition/retrieval produced by morphine sensitization phenomenon. In contrast, microinjection of subthreshold doses of SB-334867 (10, 20 and 40 nmol/rat) into the CA1 region in the training session, 5 min prior to morphine (5 mg/kg, s.c.; expression phase for morphine sensitization) blocked the spatial memory acquisition/retrieval in morphine-sensitized rats. In conclusion, these findings show that morphine sensitization reverses morphine-induced amnesia. Furthermore, the blockade of CA1 OX1Rs in the expression phase, but not in the induction phase, disrupts memory restoration induced by morphine sensitization.
    No preview · Article · Nov 2015 · Neuroscience
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    ABSTRACT: Excessive playing of computer games like some other behaviors could lead to addiction. Addictive behaviors may induce their reinforcing effects through stimulation of the brain dopaminergic mesolimbic pathway. The status of dopamine receptors in the brain may be parallel to their homologous receptors in peripheral blood lymphocytes (PBLs). Here, we have investigated the mRNA expression of dopamine D3, D4 and D5 receptors in PBLs of computer game addicts (n = 20) in comparison to normal subjects (n = 20), using a real-time PCR method. The results showed that the expression level of D3 and D4 dopamine receptors in computer game addicts were not statistically different from the control group. However, the expression of the mRNA of D5 dopamine receptor was significantly down-regulated in PBLs of computer game addicts and reached 0.42 the amount of the control group. It is concluded that unlike with drug addiction, the expression levels of the D3 and D4 dopamine receptors in computer game addicts are not altered compared to the control group. However, reduced level of the D5 dopamine receptor in computer game addicts may serve as a peripheral marker in studies where the confounding effects of abused drugs are unwanted.
    Full-text · Article · May 2015 · Journal of Neural Transmission
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    ABSTRACT: The roles of GABAergic receptors of the Basolateral amygdala (BLA) in the cannabinoid CB1 receptor agonist (arachydonilcyclopropylamide; ACPA)-induced anxiolytic-like effect and aversive memory deficit in adult male mice were examined in elevated plus-maze task. Results showed that pre-test intra-peritoneal injection of ACPA induced anxiolytic-like effect (at dose of 0.05 mg/kg) and aversive memory deficit (at doses of 0.025 and 0.05 mg/kg). The results revealed that Pre-test intra-BLA infusion of muscimol (GABAA receptor agonist; at doses of 0.1 and 0.2 µg/mouse) or bicuculline (GABAA receptor antagonist; at all doses) impaired and did not alter aversive memory, respectively. All previous GABA agents did not have any effects on anxiety-like behaviors. Interestingly, pretreatment with a sub-threshold dose of muscimol (0.025 µg/mouse) and bicuculline (0.025 µg/mouse) did not alter anxiolytic-like behaviors induced by ACPA, while both drugs restored ACPA-induced amnesia. Moreover, muscimol or bicuculline increased and decreased ACPA-induced locomotor activity, respectively. Finally the data may indicate that BLA GABAA receptors have critical and different roles in an-xiolytic-like effect, aversive memory deficit and locomotor activity induced by ACPA. © 2015, Leibniz Research Centre for Working Environment and Human Factors. All rights reserved.
    Preview · Article · May 2015 · EXCLI Journal
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    N. Vousooghi · M.S.S. Shirazi · A. Goodarzi · P.H. Abharian · M.-R. Zarrindast
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    ABSTRACT: 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.
    Full-text · Article · Jan 2015
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    Payvand Bina · Mehrnaz Rezvanfard · Shamseddin Ahmadi · Mohammad Reza Zarrindast
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    ABSTRACT: Introduction: In this study, we investigated the role of N-Methyl-D-Aspartate (NMDA) receptors in the ventral hippocampus (VH) and their possible interactions with GABA A system on anxiety-like behaviors. Methods: We used an elevated-plus maze test (EPM) to assess anxiety-like behaviors and locomotor activity in male Wistar rats. Results: The results showed that intra-VH infusions of different doses of NMDA (0.25 and 0.5 µg/rat) increased locomotor activity, and also induced anxiolytic-like behaviors, as revealed by a tendency to increase percentage of open arm time (%OAT), and a significant increase in percentage of open arm entries (%OAE). The results also showed that intra-VH infusions of muscimol (0.5 and 1 µg/rat) or bicuculline (0.5 and 1 µg/rat) did not significantly affect anxiety-like behaviors, but bicuculline at dose of 1 µg/rat increased locomotor activity. Intra-VH co-infusions of muscimol (0.5 µg/rat) along with low doses of NMDA (0.0625 and 0.125 µg/rat) showed a tendency to increase %OAT, %OAE and locomotor activity; however, no interaction was observed between the drugs. Interestingly, intra-VH co-infusions of bicuculline (0.5 µg/rat) along with effective doses of NMDA (0.25 and 0.5 µg/rat) decreased %OAT, %OAE and locomotor activity, and a significant interaction between two drugs was observed. Discussion: It can be concluded that GABAergic system may mediate the anxiolytic-like effects and increase in locomotor activity induced by NMDA in the VH.
    Full-text · Article · Nov 2014 · Basic and Clinical Neuroscience
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    ABSTRACT: The interaction between antinociception induced by CB1 agonist and muscarinic receptor modulators has not been studied yet. In the present study, the effect of pilocarpine (a muscarinic agonist) and atropine (a muscarinic antagonist) on arachidonylcyclopropylamide (ACPA, a CB1 agonist) induced antinociception was studied in mice. In this study the antinociceptive effect of intracerebroventricular administration of ACPA (0.001–2 μg/mice) or intraperitoneal injection of pilocarpine (2.5–20 mg/kg) or atropine (1 and 5 mg/kg) were studied individually. Then the effect of co-administration of pilocarine (2.5 mg/kg) or atropine (5 mg/kg) and ACPA (0.001–2 μg/mice) were studied as well. ACPA and pilocarpine induced antinociception in mice but atropine did not. Pilocarpine potentiated but atropine antagonized the antinociceptive effect of ACPA. It is concluded that ACPA induced antinociception is influenced by muscarinic receptor modulators in mice.
    Full-text · Article · Oct 2014 · Physiology & Behavior
  • Nasrin Hosseini · Hojjatallah Alaei · Mohammad Reza Zarrindast · Mohammad Nasehi · Maryam Radahmadi
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    ABSTRACT: Background: There is evidence that cognitive functions are affected by some liver diseases such as cholestasis. Bile duct ligation induces cholestasis as a result of impaired liver function and cognition. This research investigates the effect of cholestasis progression on memory function in bile duct ligation rats. Materials and Methods: Male Wistar rats were randomly divided into five groups, which include: control group for BDL-7, control group for BDL-21, sham group (underwent laparotomy without bile duct ligation), BDL-7 group (7 days after bile duct ligation), and BDL-21 group (21 days after bile duct ligation). Step-through passive avoidance test was employed to examine memory function. In all groups, short-term (7 days after foot shock) and long-term memories (21 days after foot shock) were assessed. Results: Our results showed that liver function significantly decreased with cholestasis progression (P < 0.01). Also our findings indicated BDL-21 significantly impaired acquisition time (P < 0.05). Memory retrieval impaired 7 (P < 0.05) and 21 days (P < 0.001) after foot shock in BDL-7 and BDL-21 groups, respectively. Conclusion: Based on these findings, liver function altered in cholestasis and memory (short-term and long-term memory) impaired with cholestasis progression in bile duct ligation rats. Further studies are needed to better insight the nature of progression of brain damage in cholestatic disease.
    No preview · Article · Oct 2014
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    Mohammad Torabi Nami · Mohammad Nasehi · Samira Razavi · Mohammad Reza Zarrindast
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    ABSTRACT: Background: Sleep deprivation (SD) is emerging as a hot topic due to its health concerns. There are compelling reasons for a tremendous interest in neuroscience of sleep in recent years.Objectives: We aimed to evaluate how total sleep deprivation (TSD) and chronic partial sleep restriction (CPSR) might affect memory, anxiety-related behaviors, and the serum level of neurochemical markers such as brain-derived neurotrophic factor (BDNF) and corticosterone in a rat model.Materials and Methods: The disk-over-water (DOW) apparatus was employed to induce TSD and CPSR in male Wistar rats. The six study arms were as follows: cage control, 48 hours; cage control, seven days; DOW control, 48 hours; DOW control, seven days, TSD, and CPSR. Elevated plus-maze (EPM) was used to measure parameters (percentage of OAT, percentage of OAE, and locomotor activity) corresponding to anxiety and aversive memory. To measure serum BDNF and corticosterone levels using the ELISA method, blood samples were drawn from all rats on the fourth day at 5 P.M.Results: Our results demonstrated that TSD (P < 0.001) and CPSR (P < 0.001) induce memory impairment while exert anxiolytic-like effects in comparison with controls. Data showed that CPSR causes more memory impairment and anxiolytic-like effect in comparison to TSD (P < 0.001).These interventions however, did not alter the locomotor activity. Serum corticosterone level raised dramatically in CPSR rats in comparison to TSD and controls. Although the difference in serum BDNF level between TSD and CPSRarms was insignificant, it was markedly decreased in comparison to corresponding controls (P < 0.001).Conclusions: Our findings suggest the more pronounced effect of CPSR rather than TSD in impairing aversive memory and reducing anxiety. Decreased BDNF and peaked corticosterone level in TSD and CPSR suggest the probable inflammatory processes involved in possible insults to the brain caused by SD.
    Full-text · Article · Oct 2014 · Shiraz E Medical Journal
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    ABSTRACT: Background: Early-onset Alzheimer's disease (EOAD) represents less than 5% of all AD cases. Autosomal dominant EOAD has been defined as the occurrence of at least three cases in three generations. Mutations in the amyloid precursor protein (APP), presenilin-1 and presenilin-2 genes have been recognized to be the cause of EOAD. Objective: We investigated the genotype of EOAD in two generations of two families with EOAD living in an Iranian village. Methods: The polymerase chain reaction method was used to study the presenilin-1 and APP genes in 25 subjects of these generations. Results: A guanine-to-adenine transition in exon 17 of the APP gene resulting in a valine-to-isoleucine substitution at codon 717 was detected in 14 subjects including 6 patients with EOAD. Conclusion: This mutation demonstrates the importance of γ-secretase, the necessity of early detection of patients with memory decline in the susceptible population and raising public awareness of consanguinity marriages. © 2014 S. Karger AG, Basel.
    Full-text · Article · Aug 2014 · Dementia and Geriatric Cognitive Disorders
  • Nasrin Hosseini · H Alaei · MR Zarrindast · M Nasehi · M Radahmadi

    No preview · Article · Jan 2014
  • Morteza Piri · Masoumeh Rostampour · Mohammad Nasehi · Mohammad Reza Zarrindast
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    ABSTRACT: In the present study, we investigated the possible role of the dorsal hippocampal dopamine D1 receptors on scopolamine-induced amnesia as well as scopolamine state-dependent memory in adult male Wistar rats. Animals were bilaterally implanted with chronic cannulae in the CA1 regions of the dorsal hippocampus, trained in a step-through type inhibitory avoidance task, and tested 24 h after training for their step-through latency. Results indicated that pre-training or pre-test intra-CA1 administration of scopolamine (1.5 and 3 μg/rat) dose-dependently reduced the step-through latency, showing an amnestic response. The pre-training scopolamine-induced amnesia (3 μg/rat) was reversed by the pre-test administration of scopolamine, indicating a state-dependent effect. Similarly, the pre-test administration of dopamine D1 receptor agonist, SKF 38393 (1, 2 and 4 μg/rat, intra-CA1), could significantly reverse the scopolamine-induced amnesia. Interestingly, administration of an ineffective dose of scopolamine (0.25 μg/rat, intra-CA1) before different doses of SKF 38393, blocked the reversal effect of SKF 38393 on the pre-training scopolamine-induced amnesia. Moreover, while the pre-test intra-CA1 injection of the dopamine D1 receptor antagonist, SCH 23390 (0.1 and 0.5 μg/rat, intra-CA1), resulted in apparent memory impairment, microinjection of the same doses of this agent inhibited the scopolamine-induced state-dependent memory. These results indicate that the dorsal hippocampal (CA1) dopamine D1 receptors may potentially play an important role in scopolamine-induced amnesia as well as the scopolamine state-dependent memory. Furthermore, our results propose that dopamine D1 receptor agonist, SKF 38393 reverses the scopolamine induced amnesia via acetylcholine release and possibly through the activation of muscarinic receptors.
    No preview · Article · Aug 2013 · Neuroscience
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    Morteza Piri · Elham Ayazi · Mohammad Reza Zarrindast
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    ABSTRACT: Anxiety-related behaviors increase histamine and dopamine release in the brain. On the other hand, central histamine counteracts reward and reinforcement processes mediated by the mesolimbic dopamine system. We investigated the effects of the histaminergic system and dopamine D2 receptors agents and their interactions on anxiety-related behaviors using the elevated plus-maze (EPM). The intra-hippocampal (Intra-CA1) microinjection of histamine (10μg/mouse) decreased the percentage of open arm time (%OAT) and open arm entries (%OAE) but not the locomotor activity, indicating an anxiogenic-like response. Quinpirole (0.5 and 2μg/mouse) or sulpiride (0.3 and 1μg/mouse) when injected into the dorsal hippocampus also induced anxiety-like behavior, however, the drugs reversed the anxiogenic response induced by the effective dose of histamine (10μg/mouse). Taken together and under the present experimental design, our results indicate that activation of the dorsal hippocampal histaminergic receptors causes anxiety-like behaviors altered by dopamine D2 receptor agonist and antagonist. Histamine can decrease dopaminergic tone in the dorsal hippocampus through decreasing the endogenous dopamine release, whereas quinpirole does the same via the postsynaptic DA receptors' activation. Sulpiride however renders the same effect through autoreceptors' blockade and potentiated dopamine transmission. Thus, quinpirole and sulpiride seem to compensate the effects of the intra-CA1 injection of exogenous histamine, and tend to exert anxiolytic effects in the presence of histamine.
    Preview · Article · Jul 2013 · Neuroscience Letters
  • Farhad Valizadegan · Shahrbanoo Oryan · Mohammad Nasehi · Mohammad Reza Zarrindast
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    ABSTRACT: BACKGROND: The amygdala is the key brain structure for anxiety and emotional memory storage. We examined the involvement of β-adrenoreceptors in the basolateral amygdala (BLA) and their interaction with morphine in modulating these behaviors. The elevated plus-maze has been employed for investigating anxiety and memory. Male Wistar rats were used for this test. We injected morphine (4, 5, and 6 mg/kg) intraperitoneally, while salbutamol (albuterol) (1, 2, and 4 μg/rat) and propranolol (1, 2, and 4 μg/rat) were injected into the BLA. Open- arms time percentage (%OAT), open- arms entry percentage (%OAE), and locomotor activity were determined by this behavioral test. Retention was tested 24 hours later. Intraperitoneal injection of morphine (6 mg/kg) had an anxiolytic-like effect and improvement of memory. The highest dose of salbutamol decreased the anxiety parameters in test session and improved the memory in retest session. Coadministration of salbutamol and ineffective dose of morphine presenting anxiolytic response. In this case, the memory was improved. Intra-BLA administration of propranolol (4 μg/rat) decreased %OAT in the test session, while had no effect on memory formation. Coadministration of propranolol and morphine (6 mg/kg) showed an increase in %OAT. There was not any significant change in the above- mentioned parameter in the retest session. Coadministration of morphine and propranolol with the effective dose of salbutamol showed that propranolol could reverse anxiolytic-like effect. We found that opioidergic and β-adrenergic systems have the same effects on anxiety and memory in the BLA; but these effects are independent of each other.
    No preview · Article · May 2013 · Archives of Iranian medicine
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    ABSTRACT: Background: 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. Methods: Wistar rats were used in this study. Male Wistar rats bred in an animal house, in a temperature-controlled (22±2 {ring operator} 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. Results: 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. Conclusion: Nicotinic receptors in the nucleus accumbens shell involved to anxietylike behavior in male rats.
    No preview · Article · May 2013 · Tehran University Medical Journal
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    ABSTRACT: Experimentally-induced total sleep deprivation (TSD) and chronic partial sleep restriction (CPSR) leads to the emergence of cognitive impairments. This is hypothesized to result from a consequent neuroinflammation which may also hasten the neurodegenerative processes. Neuroinflammatory markers such as tumor necrosis factor-alpha (TNFα) are thought to be potential culprits in SD-induced neurodegeneration. Methods: The effect of TSD and CPSR on memory and anxiety-related behaviors (using the Elevated Plus-Maze testretest protocol) and serum level of brain derived neurotrophic factor (BDNF) and corticosterone were assessed in male Wistar rats subjected to the modified disk-over-water (DOW)apparatus. In addition, an immunohistochemical (IHC) study was done to possibly detect the amyloid-beta (Aβ) and hyper-phosphorylated tau protein (HPτ) deposition in the dentate gyrus (DG) of the examined rats’ hippocampi. Histomorphology and neuronal numerical density assessments were done at the same level across control and experimental animals. We also studied the above parameters in rats after intraperitoneal injection of the TNFα neutralizing antibody, infliximab (IFX). Results: Rats subjected to TSD and CPSR which did not receive IFX, showed a more pronounced impairment of memory, elevated serum corticosterone and decreased BDNF levels. CPSR rats which underwent delayed brain excision following behavioral testing, showed deposition of the HPτ and revealed the least numerical density in the hippocampal DG neurons. Meanwhile, IHC study revealed no Aβ deposition in the hippocampal DG of all examined rats. Interestingly, treatment with IFX, abrogated sleep restriction-induced cognitive decline, biochemical changes and the immunohistopathology in the hippocampal DG. Conclusions: Taken together, our findings indicated that CPSR (the SD model mimicking shift work) induces not only cognitive and biochemical changes, but also pathology in the hippocampal DG. This is possibly via activation of the inflammatory mechanisms in part through TNFα-dependent pathways.
    Full-text · Article · Apr 2013 · EXCLI Journal
  • M. Torabi-Namia · M. Nasehie · M.-R. Zarrindast
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    ABSTRACT: Background: Experimentally-induced total sleep deprivation (TSD) and chronic partial sleep restriction (CPSR) leads to the emergence of cognitive impairments. This is hypothesized to result from a consequent neuroinflammation which may also hasten the neurodegenerative processes. Neuroinflammatory markers such as tumor necrosis factor-alpha (TNFα) are thought to be potential culprits in SD-induced neurodegeneration. Methods: The effect of TSD and CPSR on memory and anxiety-related behaviors (using the Elevated Plus-Maze testretest protocol) and serum level of brain derived neurotrophic factor (BDNF) and corticosterone were assessed in male Wistar rats subjected to the modified disk-over-water (DOW) apparatus. In addition, an immunohistochemical (IHC) study was done to possibly detect the amyloid-beta (Aβ) and hyper-phosphorylated tau protein (HPτ) deposition in the dentate gyrus (DG) of the examined rats' hippocampi. Histomorphology and neuronal numerical density assessments were done at the same level across control and experimental animals. We also studied the above parameters in rats after intraperitoneal injection of the TNFα neutralizing antibody, infliximab (IFX). Results: Rats subjected to TSD and CPSR which did not receive IFX, showed a more pronounced impairment of memory, elevated serum corticosterone and decreased BDNF levels. CPSR rats which underwent delayed brain excision following behavioral testing, showed deposition of the HPτ and revealed the least numerical density in the hippocampal DG neurons. Meanwhile, IHC study revealed no Aβ deposition in the hippocampal DG of all examined rats. Interestingly, treatment with IFX, abrogated sleep restriction- induced cognitive decline, biochemical changes and the immunohistopathology in the hippocampal DG. Conclusions: Taken together, our findings indicated that CPSR (the SD model mimicking shift work) induces not only cognitive and biochemical changes, but also pathology in the hippocampal DG. This is possibly via activation of the inflammatory mechanisms in part through TNFα-dependent pathways.
    No preview · Article · Apr 2013 · EXCLI Journal
  • Mohammad Nasehi · Morteza Piri · Kobra Abbolhasani · Mohammad R Zarrindast
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    ABSTRACT: Bile duct ligation (BDL) is an animal model used in cholestatic disease research. Both opioidergic and nitrergic systems are known to be involved in cholestasis. The aim of this study was to investigate the possible interaction between these two systems in BDL-induced memory formation and exploratory behaviors in mice. Male mice weighing 25-30 g were divided into nonoperated controls, sham-operated, and BDL groups. One-trial step-down and hole-board paradigms were used to assess memory acquisition and exploratory behaviors, respectively. Cholestasis did not alter memory acquisition while increasing exploratory behaviors 7 days after BDL. A pretraining intraperitoneal injection of L-arginine (50, 100, and 200 mg/kg), L-NG-nitroarginine methyl ester (L-NAME) (5, 10, 20, and 40 mg/kg), or naloxone (0.125, 0.25, and 0.5 mg/kg) did not alter memory acquisition or exploratory behaviors, whereas morphine (5 and 7.5 mg/kg) decreased memory acquisition in sham-operated animals. Moreover, although injection of L-NAME and naloxone exerted no effect on memory acquisition in the 7 days post-BDL mice, L-arginine (100 and 200 mg/kg) and morphine (2.5, 5, and 7.5 mg/kg) injection reduced it. In contrast, L-NAME and naloxone, but not morphine or L-arginine, reduced the BDL-induced exploratory behaviors. Coadministration of subthreshold doses of morphine (1.25 mg/kg) and L-arginine (50 mg/kg) caused a memory deficit in 7 days post-BDL mice. However, the memory deficit induced by the effective doses of morphine (2.5 mg/kg) or L-arginine (200 mg/kg) in these mice was restored by the administration of either naloxone (0.5 mg/kg) or L-NAME (40 mg/kg). In addition, naloxone and L-NAME reduced the exploratory behaviors in L-arginine-pretreated mice but not in morphine-pretreated mice. We conclude that there appears to be a synergistic effect between opioidergic and nitrergic systems on memory acquisition and exploratory behaviors in cholestatic mice.
    No preview · Article · Apr 2013 · Behavioural pharmacology
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    Hatam Ahmadi · Mohammad Nasehi · Parvin Rostami · Mohammad Reza Zarrindast
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    ABSTRACT: Background: Nucleus accumbens (NAc) and prefrontal cortex (PFC) dopaminergic and glutamatergic systems are involved in fear/anxiety-related behaviors; meanwhile NAc dopaminergic system activity is mediated by PFC via NAc glutamatergic projections. This study has investigated the involvement of NAc shell dopaminergic system in prelimbic NMDA-induced anxiolytic-like behaviors. Method: Elevated plus-maze apparatus was employed to test parameters of anxiety-like behaviors in male Wistar rats. Results: Unilateral intra-prelimbic injection of NMDA (0.9 μg/μl) but not D-AP7 (NMDA receptor antagonist; 0.25, 0.5 and 1 μg/μl) induced anxiolytic-like behaviors which was blocked by D-AP7. Moreover, unilateral infusion of SCH23390 (dopamine D1 receptor antagonist; 0.25, 0.5 and 1 μg/μl) and quinpirole (dopamine D2 receptor agonist; 0.125, 0.25 and 0.5 μg/μl) into the left NAc shell, did not alter anxiety-like behaviors. However, injection of SKF38393 (dopamine D1 receptor agonist; 3 μg/μl) and sulpiride (dopamine D2 receptor antagonist; 0.4 and 0.6 μg/μl) into the left NAc shell, likewise induced anxiolytic-like behaviors which were blocked by SCH23390 (0.25 μg/μl) and SKF96365 (Ca-channel blocker; 0.125 μg/μl)/SCH23390 (0.25 μg/μl), respectively. Furthermore, infusion of the subthreshold dose of SCH23390 (0.25 μg/μl) or quinpirole (0.25 μg/μl) into the left NAc shell, reduced while did not alter intra-prelimbic NMDA-induced anxiolytic-like behaviors, respectively. In addition, intra-NAc shell administration of the subthreshold dose of SKF38393 (1 μg/μl) or sulpiride (0.2 μg/μl), potentiated the lower dose response, while decreased the higher dose intra-left prelimbic NMDA response. Conclusion: Our results suggested a modulatory effect of the NAc shell dopaminergic system on prelimbic NMDA-induced anxiolytic-like behaviors.
    Full-text · Article · Apr 2013 · Neuropharmacology
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    Mohammad Nasehi · Samaneh Amin Yavari · Mohammad Reza Zarrindast
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    ABSTRACT: Background and aim: Numerous investigations have indicated that hepatic encephalopathy (HE) alters the levels of various neurotransmitters. However, comprehensive data regarding the effects of CA1 opioidergic and dopaminergic (DAergic) systems on HE-induced amnesia are still lacking. Methods: Following intra-dorsal hippocampal (CA1) injection of mu opioid and dopamine D1- and D2-like receptors antagonists in male mice, one-trial step-down and hole-board paradigms were used to assess memory and exploratory behaviors, respectively. Results: Our data demonstrated that HE impairs memory 24 days after bile duct ligation (BDL). Furthermore, while the higher dose of DA D1-like receptor antagonist (SCH23390, 0.5 μg/mouse) induced amnesia and anxiogenic-like behaviors, mu receptor antagonist (naloxone: 0.0125, 0.025 and 0.05 μg/mouse) and DA D2-like receptor antagonist (sulpiride: 0.0625, 0.125 and 0.25 μg/mouse) by themselves, could not exert an effect on memory performance in passive avoidance task. On the other hand, pre-test injection of all drugs reversed the HE-induced amnesia 24 days after BDL, while having no effect on exploratory behaviors. Pre-test co-administration of the subthreshold dose SCH23390 (0.25 μg/mouse) and sulpiride (0.0625 μg/mouse) or naloxone (0.0125 μg/mouse) could likewise reverse the BDL-induced amnesia. However, when the subthreshold sulpiride plus naloxone were co-administered, BDL-induced amnesia was not blocked. Conclusions: Memory performance is impaired 24 days post BDL and CA1 mu opioid and DA D1-like receptors antagonist synergistic effects are likely involved in this phenomenon.
    Full-text · Article · Feb 2013 · Psychopharmacology

Publication Stats

3k Citations
515.37 Total Impact Points

Institutions

  • 2009-2015
    • Institute for Research in Fundamental Sciences (IPM)
      • School of Cognitive Sciences
      Teheran, Tehrān, Iran
  • 1989-2015
    • Tehran University of Medical Sciences
      • • Department of Pharmacology
      • • School of Advanced Technologies in Medicine
      • • School of Medicine
      Teheran, Tehrān, Iran
  • 2014
    • National Institute of Genetic Engineering and Biotechnology
      Teheran, Tehrān, Iran
  • 2011-2013
    • Institute for Cognitive Science Studies
      Teheran, Tehrān, Iran
  • 2007-2011
    • Institute for Cognitive Sciences Studies
      Teheran, Tehrān, Iran
    • Zanjan University of Medical Sciences
      • Department of Pharmacology and Toxicology
      Zanjān, Zanjan, Iran
  • 1987-2007
    • University of Tehran
      • Department of Pharmacology
      Teheran, Tehrān, Iran
  • 2003
    • Iran University of Medical Science
      Teheran, Tehrān, Iran
  • 1999
    • Shahid Beheshti University of Medical Sciences
      • Department of Pharmacology
      Teheran, Tehrān, Iran
  • 1997
    • Tarbiat Modares University
      • Department of Physiology
      Tehrān, Ostan-e Tehran, Iran
    • Dalhousie University
      • Department of Pharmacology
      Halifax, Nova Scotia, Canada