Institute for Cognitive Science Studies

Tehrān, Iran

Institute for Cognitive Science Studies

Tehrān, Iran
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Burke D.A.,Duke University | Heshmati P.,Institute for Cognitive Science Studies | Kholdebarin E.,Duke University | Levin E.D.,Duke University
European Journal of Pharmacology | Year: 2014

Nicotinic systems have been shown by a variety of studies to be involved in cognitive function. Nicotinic receptors have an inherent property to become desensitized after activation. The relative role of nicotinic receptor activation vs. net receptor inactivation by desensitization in the cognitive effects of nicotinic drugs remains to be fully understood. In these studies, we tested the effects of the α7 nicotinic receptor antagonist methyllycaconitine (MLA), the α4β2 nicotinic receptor antagonist dihydro-β-erythroidine (DHβE), the nonspecific nicotinic channel blocker mecamylamine and the α4β2 nicotinic receptor desensitizing agent sazetidine-A on learning in a repeated acquisition test. Adult female Sprague-Dawley rats were trained on a repeated acquisition learning procedure in an 8-arm radial maze. MLA (1-4 mg/kg), DHβE (1-4 mg/kg), mecamylamine (0.125-0.5 mg/kg) or sazetidine-A (1 and 3 mg/kg) were administered in four different studies either alone or together with the NMDA glutamate antagonist dizocilpine (0.05 and 0.10 mg/kg). MLA significantly counteracted the learning impairment caused by dizocilpine. The overall choice accuracy impairment caused by dizocilpine was significantly attenuated by co-administration of DHβE. Low doses of the non-specific nicotinic antagonist mecamylamine also reduced dizocilpine-induced repeated acquisition impairment. Sazetidine-A reversed the accuracy impairment caused by dizocilpine. These studies provide evidence that a net decrease in nicotinic receptor activity can improve learning by attenuating learning impairment induced by NMDA glutamate blockade. This adds to evidence in cognitive tests that nicotinic antagonists can improve cognitive function. Further research characterizing the efficacy and mechanisms underlying nicotinic antagonist and desensitization induced cognitive improvement is warranted. © 2014 Elsevier B.V.


Zarrindast M.R.,Tehran University of Medical Sciences | Zarrindast M.R.,Institute for Research in Fundamental Sciences | Zarrindast M.R.,Institute for Cognitive Science Studies | Aghamohammadi-Sereshki A.,University of Tehran | And 2 more authors.
Journal of Psychopharmacology | Year: 2012

The objective of the present study was to investigate the possible role of the N-methyl-D-aspartate (NMDA) receptor system of the central amygdala (CeA) in the anxiogenic-like effect of nicotine. Male Wistar rats with cannulas aimed to the CeA were submitted to the elevated plus-maze (EPM). Intraperitoneal (i.p.) injections of nicotine (0.6 and 0.8 mg/kg) decreased percentage open arm time spent (%OAT) and percentage open arm entries (%OAE), but not locomotor activity, indicating an anxiogenic-like response. Bilateral intra-CeA microinjection of NMDA (0.005-0.1 μ g/rat) decreased %OAT, but not %OAE and locomotor activity. Moreover, intra-CeA microinjection of NMDA (0.05 μ g) with an ineffective dose of nicotine (0.4 mg/kg, i.p.) reduced %OAT and %OAE without effect on locomotor activity. On the other hand, intra-CeA microinjection of the NMDA receptor antagonist D-AP5 (0.05-0.5 μ g/rat) increased both %OAT and %OAE, showing an anxiolytic-like effect of the drug. Co-administration of the same doses of D-AP5 with nicotine (0.6 mg/kg, i.p.) increased %OAT and %OAE, but not locomotor activity. Intra-CeA microinjection of D-AP5 reversed the response induced by NMDA (0.1 μ g/rat) in the EPM. The results may support the possible involvement of glutamate transmission, through NMDA receptors of central amygdala in the anxiogenic-like effect of nicotine in the EPM task. © The Author(s) 2012.


Zarrindast M.R.,Tehran University of Medical Sciences | Zarrindast M.R.,Institute for Research in Fundamental Sciences | Zarrindast M.R.,Institute for Cognitive science Studies | Piri M.,Islamic Azad University at Ardabil | And 2 more authors.
Pharmacology Biochemistry and Behavior | Year: 2012

In the present study, the possible effect of nitric oxide agents injected into the nucleus accumbens (NAc) in the presence or absence of nicotine on morphine state-dependent memory in adult male Wistar rats was investigated. As a model of memory, a step-through type inhibitory avoidance task was used. Post-training injection of morphine (4 and 6 mg/kg) dose dependently induced the impairment of memory retention. Administration of morphine (4 and 6 mg/kg) before retention induced state-dependent retrieval of the memory acquired under post-training morphine (6 mg/kg) influence. Injection of nicotine before retention (0.25 and 0.5 mg/kg) alone and nicotine (0.1, 0.25 and 0.5 mg/kg) plus an ineffective dose of morphine (2 mg/kg) reversed the post-training morphine-induced memory impairment. The amnesia elicited by morphine (6 mg/kg) was also prevented by pre-retention intra-NAc administration of a nitric oxide synthase (NOS) inhibitor, l-NAME (0.24 μg/rat, intra-NAc). Interestingly, an ineffective dose of nicotine (0.1 mg/kg) in combination with low doses of l-NAME (0.06 and 0.12 μg/rat, intra-NAc) synergistically improved memory performance impaired by morphine given after training. It is important to note that intra-NAc administration of l-NAME before retention impaired memory retrieval by itself. In contrast, pre-retention administration of l-arginine, a nitric oxide (NO) precursor (0.25 and 0.5 μg/rat, intra-NAc), which had no effect alone, prevented the nicotine reversal of morphine effect on memory. The results suggest a possible role for nitric oxide of nucleus accumbens in the improving effect of nicotine on the morphine-induced amnesia and morphine state-dependent memory. © 2011 Elsevier Inc.


Nasehi M.,Islamic Azad University at Garmsar | Piri M.,Azad University | Jamali-Raeufy N.,Institute for Cognitive Science Studies | Zarrindast M.R.,Institute for Cognitive Science Studies | And 2 more authors.
Physiology and Behavior | Year: 2010

In the present study, the effects of nitric oxide agents on WIN55, 212-2 induced state-dependent memory of passive avoidance task were examined in mice. One-trial step-down paradigm was used for the assessment of memory retention in adult male NMRI mice. Post-training intra-CA1 administration of CB1 and CB2 receptor agonists, WIN55, 212-2 (0.25, 0.5 and 1μg/mouse), dose-dependently decreased memory retrieval. The memory impairment induced by post-training administration of WIN55, 212-2 (1μg/mouse) was restored by pre-test administration of the same dose of the drug (1μsg/mouse, intra-CA1), showing the WIN55, 212-2 state-dependent memory. Single intra-CA1 administration of l-arginine (0.3, 1 and 3μg/mouse) or L-NAME (0.3, 1 and 3μg/mouse), 5. min pre-test could not alter memory retrieval. On the other hand, in the animals in which retrieval was impaired due to post-training administration of WIN55, 212-2 (1μg/mouse), pre-test intra-CA1 administration of l-arginine (1 and 3μg/mouse), but not L-NAME (0.3, 1 and 3μg/mouse) 24. h after training restored memory retrieval. Also, in the animals which received both post-training (1μg/mouse) and pre-test injections of WIN55, 212-2 (1μg/mouse), the injection of L-NAME (3μg/mouse, intra-CA1), 2. min before pre-test administration decreased retrieval. Furthermore, in the animals under the influence of post-training administration of WIN55, 212-2 (1μg/mouse), pre-test co-administration of non-effective doses of WIN55, 212-2 (0.25μg/mouse) and l-arginine (0.3 and 1μg/mouse), increased the restoration of memory by pre-test WIN55, 212-2. These findings may demonstrate the involvement of NO in state-dependent memory induced by intra-CA1 administration of WIN55, 212-2. © 2010 Elsevier Inc.


Zarrindast M.R.,Tehran University of Medical Sciences | Zarrindast M.R.,Institute for Studies in Fundamental science IPM | Zarrindast M.R.,Institute for Cognitive Science Studies | Mahboobi S.,Tehran University of Medical Sciences | And 2 more authors.
Journal of Psychopharmacology | Year: 2011

In the present study the influence of the dopaminergic system(s) of the amygdala on the anxiolytic-like effect of the cannabinoid CB1 receptor agonist, arachydonilcyclopropylamide (ACPA), in male Wistar rats was investigated. An elevated plus-maze test of anxiety was used to assess anxiety-like behaviors. The results showed that bilateral intra-amygdala injections of ACPA (0.125, 1.25 and 5 ng/rat) and the mixed dopamine D1/D2 receptor agonist, apomorphine, at different doses (0.001, 0.01 and 0.1 μg/rat) increased percentage open arm time (%OAT) and percentage open arm entries (%OAE), indicating an anxiolytic-like effect for both of the drugs. In contrast, intra-amygdala administration of the dopamine D1 receptor antagonist SCH23390 (0.5 and 1 μg/rat) and the dopamine D2 receptor antagonist, sulpiride (2 and 3 μg/rat) decreased %OAT and %OAE, suggesting an anxiogenic-like effect for both of the drugs. Interestingly, pretreatment with a sub-effective dose of apomorphine (0.0005 μg/rat) increased, while SCH23390 (0.25 μg/rat) and sulpiride (1.5 μg/rat) decreased the anxiolytic-like effect of ACPA. It can be concluded that the dopaminergic system of the amygdala may be involved, at least partly, in the anxiolytic-like effects induced by ACPA in the rat amygdala. © 2011 The Author(s).


Fasihpour B.,Tehran University of Medical Sciences | Molavi S.,Institute for Cognitive Science Studies | Molavi S.,Tehran University of Medical Sciences | Shariat S.V.,Tehran University of Medical Sciences
Journal of Mental Health | Year: 2013

Background: An epidemic of methamphetamine use has begun in Iran in recent years and psychiatric emergency services are overloaded with patients with methamphetamine-induced psychosis (MIP). Aims: To define the clinical features of inpatients with MIP in a psychiatric hospital. Method: The files of all MIP patients admitted to Iran Psychiatric Hospital located in Tehran from April 2008 to April 2010 were assessed. Data related to psychotic episode, substance use, previous psychiatric history and demographic data of 111 MIP patients were extracted and analyzed using descriptive statistical methods. Results: The most prevalent psychotic symptoms were persecutory delusion (82%), auditory hallucination (70.3%), reference delusion (57.7%), visual hallucination (44.1%), grandiosity delusion (39.6%) and jealousy delusion (26.1%). The mean duration of admission and psychotic episode was 21.43 and 17.37 days, respectively. In seven cases (8.75%), symptoms continued for more than one month. Conclusion: Frequency of psychotic symptoms in this study is relatively similar to previous studies. However, some clinical determinants such as latency of psychosis from first use and the course of psychosis are more similar to the first epidemic of methamphetamine in Japan than to more recent epidemics; which could be due to the short history of methamphetamine use in Iran. © 2013 Informa UK, Ltd.


Moradi A.R.,Kharazmi University | Moradi A.R.,Institute for Cognitive Science Studies | Moshirpanahi S.,Kharazmi University | Parhon H.,Kharazmi University | And 5 more authors.
Behaviour Research and Therapy | Year: 2014

Poor autobiographical memory specificity is a cognitive marker of posttraumatic stress disorder (PTSD) and an independent predictor of poor prognosis. This pilot randomized controlled trial investigated the efficacy of MEmory Specificity Training (MEST) (an intervention aimed at ameliorating specificity problems) on autobiographical memory recall and PTSD symptoms. Iranian combat veterans with PTSD were randomly assigned into the MEST (. n=12) or control (. n=12) group. At baseline, groups completed Farsi versions of the Autobiographical Memory Test and Impact of Event Scale-Revised. The intervention group then had four, weekly, group sessions of MEST. The control group had no additional contact. All measures were re-administered post-intervention and at three-month follow-up. The MEST group generated significantly more specific memories and had significantly fewer PTSD symptoms following training and at follow-up than the control group. Findings suggest MEST is a promising intervention for the treatment of PTSD. © 2014 Elsevier Ltd.


Solati J.,Islamic Azad University at Karaj | Zarrindast M.-R.,Islamic Azad University at Karaj | Zarrindast M.-R.,Tehran University of Medical Sciences | Zarrindast M.-R.,Institute for Studies in Theoretical Physics and Mathematics | Salari A.-A.,Institute for Cognitive Science Studies
Psychiatry and Clinical Neurosciences | Year: 2010

Aims: In the present study, we investigated the possible influence of the opioidergic system of the dorsal hippocampus on anxiety-like behaviors. Methods: Elevated plus-maze, which is one of the methods used for testing anxiety, was used in the present study. Rats were anesthetized with ketamine and xylazine and special cannulas were inserted stereotaxically into the CA1 region of the dorsal hippocampus. After 1 week of recovery, the effects of intra-CA1 administration of morphine (0.25, 0.5, 1 and 2 μg/rat; 1 μl/rat; 0.5 μl/in each side), naloxone (2, 4, 6 and 8 μg/rat), enkephalin (1, 2, 5 and 10 μg/rat) and naltrindole (0.25, 0.5, 1 and 2 μg/rat) on percentage open arm time (%OAT) and percentage open arm entries (%OAE) were determined. Results: Bilateral administration of morphine into CA1 decreases %OAT and %OAE, indicating an anxiogenic-like effect. Intra-CA1 injection of naloxone, an opioid receptor antagonist, increased both %OAT and %OAE, parameters of anxiolytic-like behavior. Bilateral administration of δ-opioid receptor agonist, [D-Pen2,5]-enkephalin acetate hydrate into the CA1, induced an anxiolytic-like effect. Furthermore, intra-CA1 injection of δ-opioid receptor antagonist, naltrindole hydrochloride, increased anxiety-related behaviors. Conclusions: The results of the present study demonstrate that activation of μ-opioid receptors in this area produce an anxiogenic response while activation of δ-opioid receptors produces an anxiolytic response. © 2010 The Authors. Psychiatry and Clinical Neurosciences © 2010 Japanese Society of Psychiatry and Neurology.


Sardari M.,University of Tehran | Rezayof A.,University of Tehran | Khodagholi F.,Shahid Beheshti University of Medical Sciences | Zarrindast M.-R.,Tehran University of Medical Sciences | And 2 more authors.
International Journal of Neuropsychopharmacology | Year: 2014

The present study was designed to investigate the involvement of GABA-A receptors of the basolateral amygdala (BLA) in the impairing effect of acute stress on memory retrieval. The BLAs of adult male Wistar rats were bilaterally cannulated and memory retrieval was measured in a step-through type passive avoidance apparatus. Acute stress was evoked by placing the animals on an elevated platform for 10, 20 and 30 min. The results indicated that exposure to 20 and 30 min stress, but not 10 min, before memory retrieval testing (pre-test exposure to stress) decreased the step-through latency, indicating stress-induced memory retrieval impairment. Intra-BLA microinjection of a GABA-A receptor agonist, muscimol (0.005-0.02 μg/rat), 5 min before exposure to an ineffective stress (10 min exposure to stress) induced memory retrieval impairment. It is important to note that pre-test intra-BLA microinjection of the same doses of muscimol had no effect on memory retrieval in the rats unexposed to 10 min stress. The blockade of GABA-A receptors of the BLA by injecting an antagonist, bicuculline (0.4-0.5 μg/rat), 5 min before 20 min exposure to stress, prevented stress-induced memory retrieval. Pre-test intra-BLA microinjection of the same doses of bicuculline (0.4-0.5 μg/rat) in rats unexposed to 20 min stress had no effect on memory retrieval. In addition, pre-treatment with bicuculline (0.1-0.4 μg/rat, intra-BLA) reversed muscimol (0.02 μg/rat, intra-BLA)-induced potentiation on the effect of stress in passive avoidance learning. It can be concluded that pre-test exposure to stress can induce memory retrieval impairment and the BLA GABA-A receptors may be involved in stress-induced memory retrieval impairment. © CINP 2013.


Mohammadzaheri F.,Hamadan University of Medical Sciences | Koegel L.K.,University of California at Santa Barbara | Rezaee M.,Hamadan University of Medical Sciences | Rafiee S.M.,Institute for Cognitive Science Studies
Journal of Autism and Developmental Disorders | Year: 2014

Accumulating studies are documenting specific motivational variables that, when combined into a naturalistic teaching paradigm, can positively influence the effectiveness of interventions for children with autism spectrum disorder (ASD). The purpose of this study was to compare two applied behavior analysis (ABA) intervention procedures, a naturalistic approach, pivotal response treatment (PRT) with a structured ABA approach in a school setting. A randomized clinical trial design using two groups of children, matched according to age, sex and mean length of utterance was used to compare the interventions. The data showed that the PRT approach was significantly more effective in improving targeted and untargeted areas after 3 months of intervention. The results are discussed in terms of variables that produce more rapid improvements in communication for children with ASD. © 2014, Springer Science+Business Media New York.

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