Publications by authors named "Nasim Vousooghi"

46 Publications

Evaluation of CART peptide level in rat plasma and CSF: Possible role as a biomarker in opioid addiction.

Peptides 2016 10 24;84:1-6. Epub 2016 Jun 24.

Genetics Laboratory, Iranian National Center for Addiction Studies (INCAS), Iranian Institute for Reduction of High-Risk Behaviors, Tehran University of Medical Sciences, Tehran, Iran; Department of Pharmacology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran; Department of Cognitive Neuroscience, Institute for Cognitive Science Studies, Tehran, Iran; Genomics Center, School of Advanced Sciences, Tehran Medical Branch, Islamic Azad University, Tehran, Iran; School of Cognitive Sciences, Institute for Studies in Theoretical Physics and Mathematics, Tehran, Iran. Electronic address:

It has been shown previously that cocaine- and amphetamine-regulated transcript (CART) peptide has a modulatory role and homeostatic regulatory effect in motivation to and reward of the drugs of abuse specially psychostimulants. Recent data also showed that in addition to psychostimulants, CART is critically involved in the different stages of opioid addiction. Here we have evaluated the fluctuations in the level of CART peptide in plasma and CSF in different phases of opioid addiction to find out whether CART can serve as a suitable marker in opioid addiction studies. Male rats were randomly distributed in groups of control, acute low-dose (10mg/kg) morphine, acute high-dose morphine (80mg/kg), chronic escalating doses of morphine, withdrawal syndrome precipitated by administration of naloxone (1mg/kg), and abstinent after long-term drug-free maintenance of addicted animals. The level of CART peptide in CSF and plasma samples was measured by enzyme immunoassay. CART peptide concentration in the CSF and plasma was significantly elevated in acute high-dose morphine and withdrawal state animals and down-regulated in addicted rats. In abstinent group, CART peptide level was up-regulated in plasma but not in CSF samples. As the observed results are in agreement with data regarding the CART mRNA and protein expression in the brain reward pathway in opioid addiction phases, it may be suggested that evaluation of CART peptide level in CSF or plasma could be a suitable marker which reflects the rises and falls of the peptide concentration in brain in the development of opioid addiction.
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http://dx.doi.org/10.1016/j.peptides.2016.06.010DOI Listing
October 2016

X Chromosome Inactivation in Opioid Addicted Women.

Basic Clin Neurosci 2015 Jul;6(3):179-84

Iranian National Center for Addiction Studies (INCAS), Iranian Institute for Reduction of High-Risk Behaviors, Tehran University of Medical Sciences, Tehran, Iran.; Department of Pharmacology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran.; Department of Cognitive Neuroscience, Institute for Cognitive Science Studies, Tehran, Iran.; Genomics Center, School of Advanced Sciences, Tehran Medical Branch, Islamic Azad University, Tehran, Iran.; School of Cognitive Sciences, Institute for Studies in Theoretical Physics and Mathematics, Tehran, Iran.

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.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4656991PMC
July 2015

Efficacy of Human Adipose Tissue-Derived Stem Cells on Neonatal Bilirubin Encephalopathy in Rats.

Neurotox Res 2016 May 27;29(4):514-24. Epub 2016 Jan 27.

Department of Neuroscience, School of Advanced Technologies in Medicine, Tehran University of Medical Sciences, Tehran, Iran.

Kernicterus is a neurological syndrome associated with indirect bilirubin accumulation and damages to the basal ganglia, cerebellum and brain stem nuclei particularly the cochlear nucleus. To mimic haemolysis in a rat model such that it was similar to what is observed in a preterm human, we injected phenylhydrazine in 7-day-old rats to induce haemolysis and then infused sulfisoxazole into the same rats at day 9 to block bilirubin binding sites in the albumin. We have investigated the effectiveness of human adiposity-derived stem cells as a therapeutic paradigm for perinatal neuronal repair in a kernicterus animal model. The level of total bilirubin, indirect bilirubin, brain bilirubin and brain iron was significantly increased in the modelling group. There was a significant decreased in all severity levels of the auditory brainstem response test in the two modelling group. Akinesia, bradykinesia and slip were significantly declined in the experience group. Apoptosis in basal ganglia and cerebellum were significantly decreased in the stem cell-treated group in comparison to the vehicle group. All severity levels of the auditory brainstem response tests were significantly decreased in 2-month-old rats. Transplantation results in the substantial alleviation of walking impairment, apoptosis and auditory dysfunction. This study provides important information for the development of therapeutic strategies using human adiposity-derived stem cells in prenatal brain damage to reduce potential sensori motor deficit.
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http://dx.doi.org/10.1007/s12640-016-9599-3DOI Listing
May 2016

Dorsal hippocampal NMDA receptors mediate the interactive effects of arachidonylcyclopropylamide and MDMA/ecstasy on memory retrieval in rats.

Prog Neuropsychopharmacol Biol Psychiatry 2016 Apr 27;66:41-47. Epub 2015 Nov 27.

Department of Neuroscience, School of Advanced Technologies in Medicine, Tehran University of Medical Sciences, Tehran, Iran; Department of Pharmacology, School of Medicine and Iranian National Center for Addiction Studies, Tehran University of Medical Sciences, Tehran, Iran; School of Cognitive Sciences, Institute for Research in Fundamental Sciences (IPM), Tehran, Iran. Electronic address:

A combination of cannabis and ecstasy may change the cognitive functions more than either drug alone. The present study was designed to investigate the possible involvement of dorsal hippocampal NMDA receptors in the interactive effects of arachidonylcyclopropylamide (ACPA) and ecstasy/MDMA on memory retrieval. Adult male Wistar rats were cannulated into the CA1 regions of the dorsal hippocampus (intra-CA1) and memory retrieval was examined using the step-through type of passive avoidance task. Intra-CA1 microinjection of a selective CB1 receptor agonist, ACPA (0.5-4ng/rat) immediately before the testing phase (pre-test), but not after the training phase (post-training), impaired memory retrieval. In addition, pre-test intra-CA1 microinjection of MDMA (0.5-1μg/rat) dose-dependently decreased step-through latency, indicating an amnesic effect of the drug by itself. Interestingly, pre-test microinjection of a higher dose of MDMA into the CA1 regions significantly improved ACPA-induced memory impairment. Moreover, pre-test intra-CA1 microinjection of a selective NMDA receptor antagonist, D-AP5 (1 and 2μg/rat) inhibited the reversal effect of MDMA on the impairment of memory retrieval induced by ACPA. Pre-test intra-CA1 microinjection of the same doses of D-AP5 had no effect on memory retrieval alone. These findings suggest that ACPA or MDMA consumption can induce memory retrieval impairment, while their co-administration improves this amnesic effect through interacting with hippocampal glutamatergic-NMDA receptor mechanism. Thus, it seems that the tendency to abuse cannabis with ecstasy may be for avoiding cognitive dysfunction.
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http://dx.doi.org/10.1016/j.pnpbp.2015.11.008DOI Listing
April 2016

mRNA expression of dopamine receptors in peripheral blood lymphocytes of computer game addicts.

J Neural Transm (Vienna) 2015 Oct 14;122(10):1391-8. Epub 2015 May 14.

Iranian National Center for Addiction Studies (INCAS), Iranian Institute for Reduction of High-Risk Behaviors, Tehran University of Medical Sciences, Tehran, Iran.

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.
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http://dx.doi.org/10.1007/s00702-015-1408-2DOI Listing
October 2015

Mu opioid receptor gene: new point mutations in opioid addicts.

Basic Clin Neurosci 2014 ;5(1):18-21

Iranian National Center for Addiction Studies, Tehran University of Medical Sciences, Tehran, Iran ; Department of Neuroscience, School of Advanced Technologies in Medicine, Tehran University of Medical Sciences, Tehran, Iran ; Department of Pharmacology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran ; Institute for Studies in Theoretical Physics and Mathematics, School of Cognitive Sciences, Tehran, Iran ; Institute for Cognitive Science Studies, Tehran, Iran.

Introduction: Association between single-nucleotide polymorphisms (SNPs) in mu opioid receptor gene and drug addiction has been shown in various studies. Here, we have evaluated the existence of polymorphisms in exon 3 of this gene in Iranian population and investigated the possible association between these mutations and opioid addiction.

Methods: 79 opioid-dependent subjects (55 males, 24 females) and 134 non-addict or control individuals (74 males, 60 females) participated in the study. Genomic DNA was extracted from volunteers' peripheral blood and exon 3 of the mu opioid receptor gene was amplified by polymerase chain reaction (PCR) whose products were then sequenced.

Results: Three different heterozygote polymorphisms were observed in 3 male individuals: 759T > C and 877G > A mutations were found in 2 control volunteers and 1043G > C substitution was observed in an opioid-addicted subject. Association between genotype and opioid addiction for each mutation was not statistically significant.

Discussion: It seems that the sample size used in our study is not enough to confirm or reject any association between 759T > C, 877G > A and 1043G > C substitutions in exon 3 of the mu opioid receptor gene and opioid addiction susceptibility in Iranian population.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4202600PMC
December 2014

Effect of NOS3 gene polymorphism on response to Tricyclic antidepressants in migraine attacks.

Iran J Neurol 2014 Jul;13(3):154-9

Department of Neuroscience, School of Advanced Technologies in Medicine, Iran University of Medical Sciences, Tehran, Iran.

Background: Migraine is a chronic neurological disorder, characterized by recurrent moderate to severe headaches. Worldwide migraine affects nearly 15%. Studies suggest that genes involved in the production of nitric oxide (NO) may act as genetic factors for migraine. NO synthase 3 (NOS3) by expressing enzyme NOS regulates endothelial derived NO. One class of medications used as first-line treatment in migraine prophylaxis is tricyclic antidepressants (TCAs). The aim of this study was to determine effects of NOS3 gene Glu298Asp polymorphism in the production of NO and response of patients to TCAs in migraine attacks.

Methods: A total of 80 migraine patients were invited to participate in the study. Patients recorded the characteristics of their migraine attacks such as frequency of attacks and intensity of headaches for the 1(st) month of the study. Then peripheral blood samples were taken from all subjects in order to determine patients' genotype distribution, mRNA expression level of NOS3 and NO content of plasma. Patients were then instructed to use 25 mg nortriptyline at night before bed for 3 months. At the end of 3(rd) month of the treatment patients again recorded the migraine characteristics for 1 month and blood sampling was performed in order to determine the level of plasma NO.

Results: The patients' genotype distribution for TT, GT, and GG was 9, 24, and 47 subjects, respectively. Mean NO level in patients with TT genotype was less in comparison to GT and GG genotypes before and after use of TCAs (P < 0.05). Mean intensity of headaches in patients with TT genotype was lower in comparison to GT and GG genotypes before and after use of TCAs (based on verbal numerical rating scale). Mean frequency of migraine attacks after use of TCAs was significantly decreased in all genotypes of NOS3 Glu298Asp polymorphism particularly in TT genotype (P < 0.05).

Conclusion: Presence of T allele of the Glu298Asp polymorphism may be a factor for TT genotype patients to produce less NO and is a favorable factor for better response to TCAs in reducing migraine attacks in comparison to GT and GG genotypes.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4240933PMC
July 2014

Early-onset Alzheimer's disease in two Iranian families: a genetic study.

Dement Geriatr Cogn Disord 2014 14;38(5-6):330-6. Epub 2014 Aug 14.

Memory and Behavioral Neurology Department (MBND), Roozbeh Hospital, Tehran, Iran.

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.
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http://dx.doi.org/10.1159/000358232DOI Listing
October 2015

The effect of tiagabine on physical development and neurological reflexes and their relationship with the γ-aminobutyric acid switch in the rat cerebral cortex during developmental stages.

Behav Pharmacol 2013 Oct;24(7):561-8

Department of Neuroscience, School of Advanced Technologies in Medicine, Tehran University of Medical Sciences, Tehran, Iran.

In the present study, we focused on γ-aminobutyric acid (GABA) signaling through the γ-aminobutyric acid transporter (GAT) in the developing rat cerebral cortex. Tiagabine was used as a GAT inhibitor. The offspring received injections from birth until postnatal day 21 intraperitoneally. Physical development and neurological reflexes were assessed daily. Tiagabine did not influence body weight, the onset and completion of incisor eruption, or the time to appearance of cliff avoidance. However, the onset and completion of eye opening, ear unfolding, and fur growth occurred earlier in treated pups. Further, the slanted board test and righting reflex showed accelerated development (i.e. decreased time to criterion) when compared with the control group. To determine whether the obtained effects are related to the GABA switch, we examined the protein and mRNA expression of the K(+)-Cl(-) cotransporter KCC2 using western blotting and RT-PCR, respectively. Downregulation of KCC2 mRNA and protein levels was observed when GAT was inhibited. The results may indicate a role of GAT in the neurobehavioral changes that accompany the developmental switch in GABA function.
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http://dx.doi.org/10.1097/FBP.0b013e328365422fDOI Listing
October 2013

Morphine-induced nitric oxide production in PC12 cells.

Arch Iran Med 2012 Jul;15(7):404-8

Department of Neuroscience, School of Advanced Medical Technologies and Department of Pharmacology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran.

Background: 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.

Methods: We used the Griess reaction to measure NO concentrations in cell culture medium.

Results: PC12 cells that were incubated for 24 h with varying concentrations of morphine (0.1, 1, 10, 100, and 1000µM) plus LPS (1 µg/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 µM morphine and for 72 h with 10,100, and 1000 µM of morphine. After 72 h, 1 µM naloxone significantly decreased NO concentration. Naloxone, at doses of 0.1, 1, and 10µM prevented NO production by 1000 µM of morphine. NMDA (0.1, 1, and 10 µM) did not alter NO concentrations after 24, 48 or 72 h. Morphine (1 µM)-induced NO production was inhibited by 10 µM NMDA after 48 h. Inhibition of NO was also noted with1 and 10 µM concentrations of morphine after 72 h.

Conclusion: 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.
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http://dx.doi.org/012157/AIM.006DOI Listing
July 2012

Involvement of the dopaminergic receptors of the rat basolateral amygdala in anxiolytic-like effects of the cholinergic system.

Eur J Pharmacol 2011 Dec 28;672(1-3):106-12. Epub 2011 Sep 28.

Department of Biology, North branch, Azad University, Tehran, Iran.

Cholinergic system stimulation in some parts of the brain may affect anxiety-related behaviors. This system has many interactions with dopaminergic neurotransmission in the brain. We have studied the effect of cholinergic system activation in the basolateral amygdala on anxiety-related behaviors in adult male wistar rats using the acetylcholinesterase inhibitor physostigmine. Furthermore, the possible involvement of dopamine D(1) and D(2) receptors of basolateral amygdala in physostigmine induced effects has been evaluated. The elevated plus-maze task was used to assess anxiety parameters and all drugs were delivered into basolateral amygdala via bilaterally implanted chronic cannulas. Physostigmine (20 μg/rat) increased the percentage of open arm time (%OAT) and open arm entries (%OAE), revealing an anxiolytic-like effect. However, muscarinic receptor antagonist scopolamine (8 μg/rat) decreased %OAT indicating anxiogenic-like effect. A sub-effective dose of scopolamine (2 μg/rat) plus physostigmine decreased %OAT and %OAE in comparison to saline plus physostigmine (20 μg/rat). Muscarinic receptor agonist pilocarpine (5 μg/rat), dopamine D(1) receptor antagonist SCH23390 (1 μg/rat) and dopamine D(2) receptor antagonist sulpiride (5 μg/rat) significantly increased %OAT which may show anxiolytic-like effects of drugs. Sulpiride (5 μg/rat) also increased %OAE parameter. Pre-treatment with SCH23390 (0.5 and 1 μg/rat) or sulpiride (5 μg/rat) blocked anxiolytic-like effect of physostigmine (20 μg/rat). All drugs were devoid of any significant effect on locomotor activity. It is concluded that intra-basolateral amygdala administration of physostigmine has anxiolytic-like effects which may be via muscarinic mechanisms. Furthermore, dopaminergic system activation probably via dopamine D(1) and D(2) receptors is necessary for mediating anxiolytic-like effects of physostigmine.
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http://dx.doi.org/10.1016/j.ejphar.2011.09.168DOI Listing
December 2011

Expression of NMDA receptor subunits in human peripheral blood lymphocytes in opioid addiction.

Eur J Pharmacol 2010 Jul 24;638(1-3):29-32. Epub 2010 Apr 24.

Science and Research Branch of Islamic Azad University, Tehran, Iran.

Glutamate receptors especially the N-methyl-D-aspartate (NMDA)-activated ones have a key role in the development and maintenance of opioid addiction. It has been proposed that the neurotransmitter receptors expression in peripheral blood lymphocytes may be parallel to their expression state in the brain. This study was designed to evaluate the possibility of using the mRNA expression state of NR2A and NR3A subunits of NMDA receptors in human peripheral blood lymphocytes as a peripheral marker in opioid addiction studies. Four groups, each comprising of 20 male individuals participated in the study: opioid addicts, methadone maintained patients, long-term abstinent former opioid addicts, and non-addicted control subjects. Real-time PCR method was used to investigate the mRNA expression level of NR2A and NR3A subunits of NMDA receptors in peripheral blood lymphocytes of all groups. Our data indicated that the mRNA expression of NR2A subunit of NMDA receptors in all three test groups was not statistically different from control subjects. However, the NR3A subunit expression was significantly down-regulated in abstinent subjects reaching 0.14 the amount of the control group. The expression of NR3A subunit was not significantly changed in addicted and methadone maintained individuals in comparison to control subjects. It is concluded that the deficiency in expression of NR3A subunit of NMDA glutamate receptors detected by a peripheral marker may be a risk factor making individuals vulnerable for opioid addiction.
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http://dx.doi.org/10.1016/j.ejphar.2010.04.017DOI Listing
July 2010

Expression of NR3B but not NR2D subunit of NMDA receptor in human blood lymphocytes can serve as a suitable peripheral marker for opioid addiction studies.

Eur J Pharmacol 2010 May 11;633(1-3):50-4. Epub 2010 Feb 11.

Science and Research Branch of Islamic Azad University, Tehran, Iran; Sina Cellular and Molecular Research Center, Tehran, Iran.

Glutamate is critically involved in opioid addiction. It has been suggested that neurotransmitter receptors expression in peripheral blood lymphocytes may reflect brain status. In the present study, using Real-time PCR, the mRNA expression of NR2D and NR3B subunits of NMDA glutamate receptor has been investigated in peripheral blood lymphocytes of four groups each comprising of 25 male individuals: opioid addicts, methadone maintained patients, long-term abstinent former opioid addicts, and non-addicted control subjects. We found that NR2D subunit mRNA expression was not changed in all three test groups in comparison to control subjects. However, the NR3B mRNA expression was significantly up-regulated by the factors 9.11 (P<0.001), 10.07 (P<0.001) and 4.08 (P<0.05) in abstinent, addicted and methadone maintained subjects, respectively relative to control group. As a conclusion, our data indicate that the transcriptional level of the NR2D subunit of NMDA receptor is not regulated by chronic opioid addiction. However, it seems that the over-expression of NR3B subunit of NMDA receptor is a long lasting result of opioid abuse. In addition, considerable decrease in the up-regulated state of the NR3B subunit by methadone may represent another benefit of methadone therapy for opioid addicts and may serve as a suitable marker to evaluate the successfulness of therapy.
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http://dx.doi.org/10.1016/j.ejphar.2010.02.007DOI Listing
May 2010

Dopamine receptors in human peripheral blood lymphocytes: changes in mRNA expression in opioid addiction.

Eur J Pharmacol 2009 Aug 13;615(1-3):218-22. Epub 2009 May 13.

Institute for Cognitive Sciences Studies, Tehran, Iran.

Gradual adaptations of the brain to repeated drug exposure may induce addiction. Brain mesolimbic dopaminergic pathway is the site of the effect of addictive drugs. The dopamine receptors in peripheral blood lymphocytes may reflect the status of homologous brain receptors. In the present study, the effects of opioid addiction on mRNA expression of dopamine D(3), D(4) and D(5) receptors in human peripheral blood lymphocytes were investigated, using a real-time PCR method. Four groups each comprising 30 individuals were enrolled in the study: opioid addicted, methadone maintained, long-term abstinent and normal subjects. The results indicated that dopamine D(3) receptor mRNA expression was increased in addicted and methadone maintained subjects by a factor of 1.74 and 1.98, respectively, but no change was observed in the abstinent group. The dopamine D(4) receptor mRNA expression was reduced in abstinent and addicted subjects (but not in the methadone group) and reached 0.44 and 0.53 the amount of the control group, respectively. Expression of dopamine D(5) receptor mRNA showed a significant reduction in abstinent subjects (0.41 the amount of the control group). However, in the addicted and methadone maintained groups, the change of expression level was not statistically significant. It can be concluded that persisting deficiency of dopamine D(4) and D(5) receptors may be a risk factor urging individuals to addiction, and methadone may exert its therapeutic effects through normalizing mRNA expression of these receptors. The dopamine D(3) receptor may have a negative feedback role in addiction; however, we have no explanation for the persisting up-regulation of this receptor in methadone subjects.
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http://dx.doi.org/10.1016/j.ejphar.2009.04.060DOI Listing
August 2009

Expression of mu opioid receptor splice variants mRNA in human blood lymphocytes: a peripheral marker for opioid addiction studies.

Int Immunopharmacol 2009 Jul 9;9(7-8):1016-20. Epub 2009 Mar 9.

Department of Pharmacology & Neuroscience Research Center, Faculty of Medicine, Shaheed Beheshti Medical University, Tehran, Iran.

The expression of the human mu opioid receptor splice variants (hMOR-1A, hMOR-1O, hMOR-1X, and hMOR-1Y) mRNA in peripheral blood lymphocytes (PBLs) was explored in opioid addicted, methadone maintained, long-term abstinent, and control subjects. Real-time PCR showed that hMOR-1X and hMOR-1Y are not expressed in PBLs. The hMOR-1A mRNA was 0.33 fold down-regulated in abstinent and 1.94 fold up-regulated in methadone maintained subjects. The hMOR-1O mRNA was down-regulated 0.39 and 0.53 fold in abstinent and methadone maintained groups, respectively. Expression of both variants in addicted group was not different from controls. It is concluded that expression of hMOR-1A and hMOR-1O variants measured by a suggested peripheral marker can serve to identify people at risk for opioid addiction and also to evaluate the successfulness of methadone therapy.
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http://dx.doi.org/10.1016/j.intimp.2009.02.010DOI Listing
July 2009

Imipramine-induced antinociception in the formalin test. Receptor mechanisms involved and effect of swim stress.

Pharmacology 2003 Jul;68(3):154-61

Department of Pharmacology, School of Medicine, Tehran University of Medical Science, Tehran, Iran.

This study concerned the effect of swim stress on imipramine-induced antinociception in mice. The data showed that intraperitoneal (i.p.) administration of different doses of imipramine (10-40 mg/kg) and 0.5-3 min of swim stress (17 degrees C) induced antinociception in the first and second phases of the formalin test. Low period of swim stress (10 s) with low doses of imipramine (2.5, 5 and 10 mg/kg i.p.), which did not have any effect by themselves, in combination showed antinociception in the second phase of the test. Either yohimbine (0.5 mg/kg i.p.) or naloxone (1 mg/kg i.p.) reversed the response induced by the combination of low doses of imipramine plus swim stress. Yohimbine (1 mg/kg i.p.) decreased the response of imipramine (20 mg/kg i.p.) but not that of 30 s swim stress in the second phase. However, naloxone (1 mg/kg i.p.) reduced the antinociception induced by imipramine (20 mg/kg i.p.) or 30 s swim stress in the second phase of the test, the combination of imipramine with swim stress was not altered by yohimbine or naloxone. Prazosin induced antinociception by itself in the first phase of the test and increased swim-stress-induced antinociception with no interaction. It is concluded that antinociception induced by imipramine in the second phase of formalin test may be mediated through alpha(2)-adrenoceptor antagonists. The results indicate that the responses of swim stress and imipramine may be mediated by an opioid mechanism, but the combination of both drugs induced higher antinociceptive effects.
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http://dx.doi.org/10.1159/000070173DOI Listing
July 2003