پیامدهای مواجهة مزمن رت‌های ماده با مرفین پیش از بارداری، بر حافظة فضایی و تمایل به مصرف مرفین فرزندان نر و ماده

نوع مقاله : مقاله پژوهشی

نویسندگان

1 دانشجوی کارشناسی‌ارشد، گروه فیزیولوژی، دانشکدة پزشکی، دانشگاه علوم پزشکی اراک، اراک، ایران

2 استادیار، گروه فیزیولوژی، دانشکدة پزشکی، دانشگاه علوم پزشکی اراک، اراک، ایران

3 دانشیار، گروه فیزیولوژی، دانشکدة پزشکی، دانشگاه علوم پزشکی اراک، اراک، ایران

4 استادیار، گروه بیوتکنولوژی و پزشکی ملکولی، دانشکدة پزشکی، دانشگاه علوم پزشکی اراک، اراک، ایران

چکیده

اهداف با توجه به افزایش سوءمصرف اپیوئیدها در بین زنان و آثار پاتوفیزیولوژیکی مواجهة مزمن اپیوئیدها بر مادران که ممکن است غیرمستقیم فرزندان آن‌ها را تحت تأثیر قراردهد، در این ‌مطالعه پیامدهای مصرف مزمن مرفین و ترک آن پیش از شروع بارداری بر حافظة فضایی، حافظة جتنابی و تمایل به مصرف مرفین فرزندان نسل اول بررسی شده است.
مواد و روش‌ها دوازده سر موش صحرایی مادة ویستار به‌صورت تصادفی به دو گروه تقسیم شد. گروه مادران مرفینی دو ماه محلول مرفین (mg/ml 4/0) و گروه مادران کنترل آب معمولی دریافت کردند. یک ماه پس از قطع مصرف مرفین جفت‌گیری ماده‌ها انجام شد. بعد از زایمان، فرزندان به‌صورت مجزا در گروه‌های نر و ماده تقسیم و به‌عنوان گروه‌های هدف مطالعه استفاده شد. حافظة فضایی با ماز آبی موریس، حافظة جتنابی با شاتل باکس و تمایل به مصرف مرفین با اندازه‌گیری مصرف اختیاری محلول مرفین بررسی شد.
یافته‌ها میانگین مصرف روزانة محلول مرفین در فرزندان نر و مادة مادران مرفینی به‌صورت معناداری بالاتر از فرزندان نر و مادة مادران کنترل بود (05/0 <P). نتایج یادگیری در ماز آبی نشان داد که فرزندان نر مادران مرفینی به‌طور معناداری نسبت به فرزندان نر گروه کنترل مسافت و زمان بیشتری را برای رسیدن به سکو صرف می‌کنند (01/0 <P). همچنین، در آزمون به‌خاطرآوری نیز فرزندان نر مادران مرفینی در مقایسه با فرزندان نر مادران کنترل دفعات کمتری از محل سکو عبور کرده‌اند (001/0 <P). تفاوت معناداری بین گروه‌های آزمایشی در میزان یادگیری اجتنابی وجود نداشت (05/0 >P).
نتیجه‌گیری مطالعة حاضر نشان داد مصرف مزمن مرفین پیش از بارداری، سبب اختلال در حافظة فضایی فرزندان نر شد. همچنین، تمایل به مصرف مرفین در فرزندان نر و ماده را افزایش داد.

کلیدواژه‌ها

موضوعات


عنوان مقاله [English]

Chronic Exposure of Female Rats with Morphine before the Gestation Causes Reduction of Spatial Memory and Increase of Vulnerability to Opiate Intake in Next Generation Offspring

نویسندگان [English]

  • Neda Moulaei 1
  • Mehdi Sadegh 2
  • Mohammad Reza Palizvan 3
  • Mahdieh Mondanizadeh 4
  • Narges-al-sadat Haeri 1
1 Master Student, Department of Physiology, Faculty of Medicine, Arak University of Medical Sciences, Arak, Iran
2 Assistant Professor, Department of Physiology, Faculty of Medicine, Arak University of Medical Sciences, Arak, Iran
3 Associate Professor, Department of Physiology, Faculty of Medicine, Arak University of Medical Sciences, Arak, Iran
4 Assistant Professor, Department of Biotechnology and Molecular Medicine, Faculty of Medicine, Arak University of Medical Sciences, Arak, Iran
چکیده [English]

Background & Objectives: According to the increasing opioids abuse between women and pathophysiological effects of chronic exposure of opioids on mothers which might indirectly affect their offspring, herein, consequences of chronic morphine consumption and its withdrawal before the gestation was investigated on spatial memory, avoidance memory and vulnerability to morphine intake in offspring of first generation.
Materials & Methods: Twelve female Wistar rats were randomly divided into two groups. Morphine mothers group received morphine solution (0.4 mg/ml) for two months. Control mothers group received tab water. One month after stopping morphine consumption, mating was occurred. After the parturition, offspring was divided in separated male and female groups and was used as the target groups of the study. Spatial memory through Water Maze, avoidance memory through Shuttle Box and vulnerability to morphine intake through voluntary consumption of morphine solution were investigated.
Results: Mean of morphine solution consumption in male and female offspring of morphine mothers was significantly higher in compare to male and female offspring of control mothers (P<0.05). Results of learning in Water Maze revealed that male offspring of morphine mothers significantly spent more time and distance to find the platform in compare with male offspring of control (P<0.01). Also, in retention test, male offspring of morphine mothers cross the location of platform significantly fewer than male offspring of control (P<0.001). There was no significant differences in avoidance learning between experimental groups (P<0.05).
Conclusion: Our study revealedchronic morphine consumption before the gestation causesdamage of spatial memory in male offspring and also increases vulnerability to opiate intake of male and female offspring.

کلیدواژه‌ها [English]

  • Addiction
  • dependence
  • Memory
  • opioids
  • Rat
1] Niu L, Cao B, Zhu H, Mei B, Wang M, Yang Y, et al. Impaired in vivo synaptic plasticity in dentate gyrus and spatial memory in juvenile rats induced by prenatal morphine exposure. Hippocampus, 2009; 19(7): 649-57.
[2] Sadegh M, Fathollahi Y, Javan M, Semnanian S. Tolerance to anti-nociceptive effects of sodium-salicylate and morphine decreases adenosine deaminase activity in the rat hippocampus. Koomesh, 2012; 13(3): 390-6.
[3] Torregrossa MM, Corlett PR, Taylor JR. Aberrant learning and memory in addiction. Neurobiol Learn Mem, 2011; 96(4): 609-23.
[4] Sadegh M, Fathollahi Y, Naghdi N, Semnanian S. Morphine deteriorates spatial memory in sodium salicylate treated rats. Eur. J. Pharmacol, 2013; 704:1-6.
[5] Simantov R. Chronic morphine alters dopamine transporter density in the rat brain: possible role in the mechanism of drug addiction. Neurosci Lett, 1993; 163(2): 121-4.
[6] Narita M, Suzuki M, Imai S, Ozaki S, Kishimoto Y, Oe K, et al. Molecular mechanism of changes in the morphine-induced pharmacological actions under chronic pain-like state: suppression of dopaminergic transmission in the brain. Life Sci, 2004; 74(21): 2655-73.
[7] Farley SJ, Radley JJ, Freeman JH. Amygdala modulation of cerebellar learning. J Neurosci, 2016; 36(7): 2190-201.
[8] McGaugh JL. Memory consolidation and the amygdala: a systems perspective. Trends Neurosci, 2002; 25(9): 456.
[9] de Hoz L, Martin SJ. Double dissociation between the contributions of the septal and temporal hippocampus to spatial learning: the role of prior experience. Hippocampus, 2014; 24(8): 990-1005.
[10] Jayaweera HK, Hickie IB, Duffy SL, Mowszowski L, Norrie L, Lagopoulos J, et al. Episodic memory in depression: the unique contribution of the anterior caudate and hippocampus. Psychol Med, 2016: 1-11.
[11] Jamot L, Matthes HW, Simonin F, Kieffer BL, Roder JC. Differential involvement of the mu and kappa opioid receptors in spatial learning. Genes Brain Behav, 2003; 2(2): 80-92.
[12] Klenowski P, Morgan M, Bartlett SE. The role of delta-opioid receptors in learning and memory underlying the development of addiction. Br J Pharmacol, 2015; 172(2): 297-310.
[13] Woods JR, Jr. Adverse consequences of prenatal illicit drug exposure. Curr Opin Obstet Gynecol, 1996; 8(6): 403-11.
[14] Sithisarn T, Granger DT, Bada HS. Consequences of prenatal substance use. Int J Adolesc Med Health, 2012; 24(2): 105-12.
[15] Glantz MD, Chambers JC. Prenatal drug exposure effects on subsequent vulnerability to drug abuse. Dev Psychopathol, 2006; 18(3): 893-922.
[16] Tan JW, Duan TT, Zhou QX, Ding ZY, Jing L, Cao J, et al. Impaired contextual fear extinction and hippocampal synaptic plasticity in adult rats induced by prenatal morphine exposure. Addict Biol, 2015; 20(4): 652-62.
[17] Robison AJ, Nestler EJ. Transcriptional and epigenetic mechanisms of addiction. Nat Rev Neurosci, 2011; 12(11): 623-37.
[18] Nestler EJ. Epigenetic mechanisms of drug addiction. Neuropharmacology, 2014; 76 Pt B:259-68.
[19] Badawy AA, Evans CM, Evans M. Production of tolerance and physical dependence in the rat by simple administration of morphine in drinking water. Br J Pharmacol, 1982; 75(3): 485-91.
[20] Sadegh M, Fathollahi Y, Naghdi N, Semnanian S. Morphine deteriorates spatial memory in sodium salicylate treated rats. Eur J Pharmacol, 2013; 704(1-3): 1-6.
[21] Cox BM, Ginsburg M, Willis J. The offset of morphine tolerance in rats and mice. Br J Pharmacol, 1975; 53(3): 383-91.
[22] Byrnes JJ, Johnson NL, Schenk ME, Byrnes EM. Cannabinoid exposure in adolescent female rats induces transgenerational effects on morphine conditioned place preference in male offspring. J Psychopharmacol, 2012; 26(10): 1348-54.
[23] Byrnes JJ, Babb JA, Scanlan VF, Byrnes EM. Adolescent opioid exposure in female rats: transgenerational effects on morphine analgesia and anxiety-like behavior in adult offspring. Behav Brain Res., 2011; 218(1): 200-5.
[24] Cicero TJ, Adams ML, Giordano A, Miller BT, O'Connor L, Nock B. Influence of morphine exposure during adolescence on the sexual maturation of male rats and the development of their offspring. J Pharmacol Exp Ther, 1991; 256(3): 1086-93.
[25] Byrnes JJ, Johnson NL, Carini LM, Byrnes EM. Multigenerational effects of adolescent morphine exposure on dopamine D2 receptor function. Psychopharmacology (Berl), 2013; 227(2): 263-72.
[26] Hyman SE. Addiction: a disease of learning and memory. Am J Psychiatry, 2005; 162(8): 1414-22.
[27] Sarkaki A, Assaei R, Motamedi F, Badavi M, Pajouhi N. Effect of parental morphine addiction on hippocampal long-term potentiation in rats offspring. Behav Brain Res, 2008; 186(1): 72-7.
[28] Yohn NL, Bartolomei MS, Blendy JA. Multigenerational and transgenerational inheritance of drug exposure: The effects of alcohol, opiates, cocaine, marijuana, and nicotine. Prog Biophys Mol Biol, 2015; 118(1-2): 21-33.
[29] Szutorisz H, DiNieri JA, Sweet E, Egervari G, Michaelides M, Carter JM, et al. Parental THC exposure leads to compulsive heroin-seeking and altered striatal synaptic plasticity in the subsequent generation. Neuropsychopharmacology, 2014; 39(6): 1315-23.
[30] Grosso A, Cambiaghi M, Concina G, Sacco T, Sacchetti B. Auditory cortex involvement in emotional learning and memory. Neuroscience, 2015; 299: 45-55.
[31] Vassoler FM, Byrnes EM, Pierce RC. The impact of exposure to addictive drugs on future generations: Physiological and behavioral effects. Neuropharmacology, 2014; 76 Pt B:269-75.
[32] Slamberova R, Schindler CJ, Pometlova M, Urkuti C, Purow-Sokol JA, Vathy I. Prenatal morphine exposure differentially alters learning and memory in male and female rats. Physiol Behav, 2001; 73(1-2): 93-103.
[33] Faraji J, Metz GA, Sutherland RJ. Characterization of spatial performance in male and female Long-Evans rats by means of the Morris water task and the ziggurat task. Brain Res Bull, 2010; 81(1): 164-72.
[34] Haeri NA, Palizvan MR, Sadegh M, Aghaei Z, Rafiei M. Prediction of seizure incidence probability in PTZ model of kindling through spatial learning ability in male and female rats. Physiol Behav, 2016; 161: 47-52.
[35] Keeley RJ, Tyndall AV, Scott GA, Saucier DM. Sex difference in cue strategy in a modified version of the Morris water task: correlations between brain and behaviour. PLoS One, 2013; 8(7): e69727.
[36] Keeley RJ, Bye C, Trow J, McDonald RJ. Strain and sex differences in brain and behaviour of adult rats: Learning and memory, anxiety and volumetric estimates. Behav Brain Res, 2015; 3(1): 118-288.
[37] Shah DS, Prados J, Gamble J, De Lillo C, Gibson CL. Sex differences in spatial memory using serial and search tasks. Behav Brain Res, 2013; 257: 90-9.
[38] Slamberova R, Rimanoczy A, Cao D, Schindler CJ, Vathy I. Alterations of prenatal morphine exposure in mu-opioid receptor density in hypothalamic nuclei associated with sexual behavior. Brain Res Bull, 2005; 65(6): 479-85.
[39] Vathy I, Katay L. Effects of prenatal morphine on adult sexual behavior and brain catecholamines in rats. Brain Res Dev Brain Res, 1992; 68(1): 125-31.
دوره 24، شماره 1
فروردین و اردیبهشت
فروردین و اردیبهشت 1396
صفحه 17-27
  • تاریخ دریافت: 29 فروردین 1395
  • تاریخ بازنگری: 23 مرداد 1395
  • تاریخ پذیرش: 03 مرداد 1395
  • تاریخ اولین انتشار: 01 فروردین 1396