Kerman University of Medical Sciences

Document Type: Original Article

Authors

1 Iranian National Center for Addiction Studies, Tehran University of Medical Sciences, Tehran, Iran

2 Iranian National Center for Addiction Studies, Tehran University of Medical Sciences, Tehran AND Department of Veterinary Medicine, Garmsar Branch, Islamic Azad University, Garmsar, Iran

3 Department of Anatomy, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran

4 Department of Biology, School of Biological Sciences, North Tehran Branch, Islamic Azad University, Tehran, Iran

5 Department of Pharmacology, School of Medicine AND Endocrinology and Metabolism Research Institute, Tehran University of Medical Sciences, Tehran, Iran

Abstract

Background: Critical analysis of new evidence in medical sciences relies on statistics in terms of correlation.
The aim of the present study was to evaluate the correlation coefficients among the behavioral features in the
offspring of morphine-abstinent parent(s).
Methods: The offspring of various types of parental morphine-exposure were divided into 4 groups including
offspring of healthy parents (CTL), offspring of paternal morphine-abstinence (PMA), offspring of maternal
morphine-abstinence (MMA), and offspring of both morphine-abstinence (BMA). Pain perception,
depression-like behavior, and avoidance memory in the offspring were quantified. The logical structure of
association was measured using the Pearson correlation analysis.
Findings: A strong correlation was observed between pain and depressive-like behavior in female and male
offspring of healthy parents. Moreover, in the male and female offspring of healthy parents and BMA, no
significant correlation was observed between avoidance memory and pain behavior or depressive-like
behavior. However, in the offspring of MMA, a strong correlation was observed between avoidance memory
and depressive-like behavior.
Conclusion: The results of the study signified the importance of correlation analysis in addictive behavior. The
results revealed that the pattern of correlation of the behavior of the offspring of MMA and PMA differed

Keywords

Shah M, Huecker MR. Opioid Withdrawal.
StatPearls. 2nd ed. Treasure Island, FL: StatPearls
Publishing; 2018.
2. Woller SA, Moreno GL, Hart N, Wellman PJ, Grau
JW, Hook MA. Analgesia or addiction?:
Implications for morphine use after spinal cord
injury. J Neurotrauma 2012; 29(8): 1650-62.
3. Li CQ, Luo YW, Bi FF, Cui TT, Song L, Cao WY,
et al. Development of anxiety-like behavior via
hippocampal IGF-2 signaling in the offspring of
parental morphine exposure: effect of enriched
environment. Neuropsychopharmacology 2014;
39(12): 2777-87.
4. Akbarabadi A, Niknamfar S, Vousooghi N, SadatShirazi MS, Toolee H, Zarrindast MR. Effect of rat
parental morphine exposure on passive avoidance
memory and morphine conditioned place preference
in male offspring. Physiol Behav 2018; 184: 143-9.
5. 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.
6. Klausz B, Pinter O, Sobor M, Gyarmati Z, Furst Z,
Timar J, et al. Changes in adaptability following
perinatal morphine exposure in juvenile and adult
rats. Eur J Pharmacol 2011; 654(2): 166-72.
7. Lu R, Liu X, Long H, Ma L. Effects of prenatal
cocaine and heroin exposure on neuronal dendrite
morphogenesis and spatial recognition memory in
mice. Neurosci Lett 2012; 522(2): 128-33.
8. DiNieri JA, Wang X, Szutorisz H, Spano SM, Kaur
J, Casaccia P, et al. Maternal cannabis use alters
ventral striatal dopamine D2 gene regulation in the
offspring. Biol Psychiatry 2011; 70(8): 763-9.
9. Vathy I. Prenatal opiate exposure: Long-term CNS
consequences in the stress system of the offspring.
Proof Version
Correlation among Behavioral Features Ahmadian-Moghadam et al.
Addict Health, Autumn 2019; Vol 11, No 4 273
http://ahj.kmu.ac.ir, 07 October
Psychoneuroendocrinology 2002; 27(1-2): 273-83.
10. Ahmadian-Moghadam H, Sadat-Shirazi1 MS,
Bobhadi-Ashar N, Seifi F, Niknamfar S, Akbarabadi
A, et al. Transgenerational influence of parental
morphine exposure on pain perception, depressivelike behavior and passive avoidance memory on the
male and female offspring of wistar rats. J Stud
Alcohol Drugs 2018. [Unpublished].
11. Becker JB, Koob GF. Sex differences in animal
models: Focus on addiction. Pharmacol Rev 2016;
68(2): 242-63.
12. Fields RD. NIH policy: Mandate goes too far. Nature
2014; 510(7505): 340.
13. Von Korff M, Simon G. The relationship between
pain and depression. Br J Psychiatry Suppl 1996;
(30): 101-8.
14. Simon CB, Lentz TA, Bishop MD, Riley JL 3 rd,
Fillingim RB, George SZ. Comparative associations
of working memory and pain catastrophizing with
chronic low back pain intensity. Phys Ther 2016;
96(7): 1049-56.
15. Compton WM, Volkow ND. Abuse of prescription
drugs and the risk of addiction. Drug Alcohol
Depend 2006; 83(Suppl 1): S4-S7.
16. Manchikanti L, Fellows B, Ailinani H, Pampati V.
Therapeutic use, abuse, and nonmedical use of
opioids: A ten-year perspective. Pain Physician
2010; 13(5): 401-35.
17. Torkaman-Boutorabi A, Seifi F, Akbarabadi A,
Toolee H, Sadat-Shirazi M, Vousooghi N, et al.
Morphine exposure and enhanced depression-like
behaviour confronting chronic stress in adult male
offspring rat. Basic Clin Neurosci 2019; 10(4):
323-32.
18. Ashabi G, Sadat-Shirazi MS, Akbarabadi A,
Vousooghi N, Kheiri Z, Toolee H, et al. Is the
nociception mechanism altered in offspring of
morphine-abstinent rats? J Pain 2018; 19(5): 529-41.
19. Sheng J, Liu S, Wang Y, Cui R, Zhang X. The Link
between Depression and Chronic Pain: Neural
mechanisms in the brain. Neural Plast 2017; 2017:
9724371.
20. Hung M, Bounsanga J, Voss MW. Interpretation of
correlations in clinical research. Postgrad Med 2017;
129(8): 902-6.
21. Stanovich KE. How to think straight about
psychology. 8th ed. Boston, MA: Pearson Allyn and
Bacon; 2007.
22. Kraemer HC. Correlation coefficients in medical
research: from product moment correlation to the
odds ratio. Stat Methods Med Res 2006; 15(6):
525-45.
23. Mukaka MM. Statistics corner: A guide to
appropriate use of correlation coefficient in medical
research. Malawi Med J 2012; 24(3): 69-71.
24. Curtis EA, Comiskey C, Dempsey O. Importance
and use of correlational research. Nurse Res 2016;
23(6): 20-5.
25. Damian JP, Acosta V, Da CM, Ramirez I, Oddone
N, Zambrana A, et al. Effect of resveratrol on
behavioral performance of streptozotocin-induced
diabetic mice in anxiety tests. Exp Anim 2014;
63(3): 277-87.
26. Motaghinejad M, Fatima S, Banifazl S, Bangash
MY, Karimian M. Study of the effects of controlled
morphine administration for treatment of anxiety,
depression and cognition impairment in morphineaddicted rats. Adv Biomed Res 2016; 5: 178.
27. Sestakova N, Puzserova A, Kluknavsky M,
Bernatova I. Determination of motor activity and
anxiety-related behaviour in rodents: methodological
aspects and role of nitric oxide. Interdiscip Toxicol
2013; 6(3): 126-35.
28. Porsolt RD, Le PM, Jalfre M. Depression: A new
animal model sensitive to antidepressant treatments.
Nature 1977; 266(5604): 730-2.
29. Hashimoto H, Hashimoto R, Shintani N, Tanaka K,
Yamamoto A, Hatanaka M, et al. Depression-like
behavior in the forced swimming test in PACAPdeficient mice: amelioration by the atypical
antipsychotic risperidone. J Neurochem 2009;
110(2): 595-602.
30. Poleszak E, Wlaz P, Kedzierska E, Nieoczym D,
Wyska E, Szymura-Oleksiak J, et al. Immobility
stress induces depression-like behavior in the forced
swim test in mice: effect of magnesium and
imipramine. Pharmacol Rep 2006; 58(5): 746-52.
31. Gawade SP. Acetic acid induced painful endogenous
infliction in writhing test on mice. J Pharmacol
Pharmacother 2012; 3(4): 348.
32. Ness TJ. Models of Visceral Nociception. ILAR J
1999; 40(3): 119-28.
33. Singh PP, Junnarkar AY, Rao CS, Varma RK,
Shridhar DR. Acetic acid and phenylquinone
writhing test: A critical study in mice. Methods Find
Exp Clin Pharmacol 1983; 5(9): 601-6.
34. Butkevich IP. Effects of prenatal stress on formalininduced acute and persistent pain in adult male rats.
Bull Exp Biol Med 2002; 133(2): 130-2.
35. Gregory NS, Harris AL, Robinson CR, Dougherty
PM, Fuchs PN, Sluka KA. An overview of animal
models of pain: Disease models and outcome
measures. J Pain 2013; 14(11): 1255-69.
36. Vousooghi N, Sadat-Shirazi MS, Safavi P, Zeraati R,
Akbarabadi A, Makki SM, et al. Adult rat morphine
exposure changes morphine preference, anxiety, and
the brain expression of dopamine receptors in male
offspring. Int J Dev Neurosci 2018; 69: 49-59.
37. Sabzevari S, Rohbani K, Sadat-Shirazi MS, BabhadiAshar N, Shakeri A, Ashabi G, et al. Morphine
Proof Version
Correlation among Behavioral Features Ahmadian-Moghadam et al.
274 Addict Health, Autumn 2019; Vol 11, No 4
http://ahj.kmu.ac.ir, 07 October
exposure before conception affects anxiety-like
behavior and CRF level (in the CSF and plasma) in
the adult male offspring. Brain Res Bull 2019; 144:
122-31.
38. Roth DA, Coles ME, Heimberg RG. The relationship
between memories for childhood teasing and anxiety
and depression in adulthood. J Anxiety Disord 2002;
16(2): 149-64.
39. Eich E, Reeves JL, Jaeger B, Graff-Radford SB.
Memory for pain: Relation between past and present
pain intensity. Pain 1985; 23(4): 375-80.
40. Crane MK, Bogner HR, Brown GK, Gallo JJ. The
link between depressive symptoms, negative
cognitive bias and memory complaints in older
adults. Aging Ment Health 2007; 11(6): 708-15.
41. Bornstein RA, Baker GB, Douglass AB. Depression
and memory in major depressive disorder. J
Neuropsychiatry Clin Neurosci 1991; 3(1): 78-80.
42. Choi DS, Choi DY, Whittington RA, Nedeljkovic
SS. Sudden amnesia resulting in pain relief: The
relationship between memory and pain. Pain 2007;
132(1-2): 206-10.
43. Arnstein PM. The neuroplastic phenomenon: a
physiologic link between chronic pain and learning. J
Neurosci Nurs 1997; 29(3): 179-86.
44. Walker EA, Keegan D, Gardner G, Sullivan M,
Bernstein D, Katon WJ. Psychosocial factors in
fibromyalgia compared with rheumatoid arthritis: II.
Sexual, physical, and emotional abuse and neglect.
Psychosom Med 1997; 59(6): 572-7.
45. Price DD. Psychological and neural mechanisms of
the affective dimension of pain. Science 2000;
288(5472): 1769-72.
46. Kahneman D, Fredrickson BL, Schreiber CA,
Redelmeier DA. When more pain is preferred to less:
Adding a better end. Psychol Sci1993; 4(6): 401-5.
47. Tasmuth T, Estlanderb AM, Kalso E. Effect of
present pain and mood on the memory of past
postoperative pain in women treated surgically for
breast cancer. Pain 1996; 68(2-3): 343-7.
48. Marsicano G, Wotjak CT, Azad SC, Bisogno T,
Rammes G, Cascio MG, et al. The endogenous
cannabinoid system controls extinction of aversive
memories. Nature 2002; 418(6897): 530-4.
49. Rodrigues SM, Schafe GE, LeDoux JE. Molecular
mechanisms underlying emotional learning and
memory in the lateral amygdala. Neuron 2004;
44(1): 75-91.
50. Dityatev AE, Bolshakov VY. Amygdala, long-term
potentiation, and fear conditioning. Neuroscientist
2005; 11(1): 75-88.
51. Frankland PW, Bontempi B, Talton LE, Kaczmarek
L, Silva AJ. The involvement of the anterior
cingulate cortex in remote contextual fear memory.
Science 2004; 304(5672): 881-3.
52. Treede RD, Apkarian AV, Bromm B, Greenspan JD,
Lenz FA. Cortical representation of pain: Functional
characterization of nociceptive areas near the lateral
sulcus. Pain 2000; 87(2): 113-9.
53. Robbins TW, Everitt BJ. Limbic-striatal memory
systems and drug addiction. Neurobiol Learn Mem
2002; 78(3): 625-36.
54. Grattan A, Sullivan MD, Saunders KW, Campbell
CI, Von Korff MR. Depression and prescription
opioid misuse among chronic opioid therapy
recipients with no history of substance abuse. Ann
Fam Med 2012; 10(4): 304-11.
55. Reid MC, Engles-Horton LL, Weber MB, Kerns RD,
Rogers EL, O'Connor PG. Use of opioid medications
for chronic noncancer pain syndromes in primary
care. J Gen Intern Med 2002; 17(3): 173-9.
56. Sullivan MD, Edlund MJ, Zhang L, Unutzer J, Wells
KB. Association between mental health disorders,
problem drug use, and regular prescription opioid
use. Arch Intern Med 2006; 166(19): 2087-93.
57. Scherrer JF, Svrakic DM, Freedland KE, Chrusciel
T, Balasubramanian S, Bucholz KK, et al.
Prescription opioid analgesics increase the risk of
depression. J Gen Intern Med 2014; 29(3): 491-9.
58. Burt DB, Zembar MJ, Niederehe G. Depression and
memory impairment: a meta-analysis of the
association, its pattern, and specificity. Psychol Bull
1995; 117(2): 285-305.
59. Volkow ND. Drug abuse and mental illness:
progress in understanding comorbidity. Am J
Psychiatry 2001; 158(8): 1181-3.
60. Edlund MJ, Martin BC, Fan MY, Braden JB,
Devries A, Sullivan MD. An analysis of heavy
utilizers of opioids for chronic noncancer pain in the
TROUP study. J Pain Symptom Manage 2010;
40(2): 279-89.
61. Volkow ND. The reality of comorbidity: depression
and drug abuse. Biol Psychiatry 2004; 56(10): 714-7.
62. Sadat-Shirazi MS, Karimi F, Kaka G, Ashabi G,
Ahmadi I, Akbarabadi A, et al. Parental morphine
exposure enhances morphine (but not
methamphetamine) preference and increases
monoamine oxidase-B level in the nucleus
accumbens. Behav Pharmacol 2019; 30(5): 435-45.