The Effect of Opium Dependency of Parent (s) on Offspring’s Spatial Learning & Memory in Adult Male Rats

Document Type: Original Article


1 Kerman Neuroscience Research Center, Kerman University of Medical Sciences Kerman, Iran

2 Department of Anatomical and Reproductive Biology, Faculty of Medical sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran

3 Mashhad Cognitive Neuroscience Research Center and Department of Physiology, Faculty ofMedical sciences, Mashhad University of Medical Sciences, Mashhad, Iran

4 Department of Physiology and Medical Student Research Committee, Faculty of Medical sciences, Shahid Beheshti University of Medical Sciences. Tehran, Iran


Objective(s):As far as we know,there has been no report regarding the effects of opium addiction or dependency of both parents on the learning and memory process in offspring. The aim of this study was to examine the learning and memory changes of adult male offspring whose mothers, fathers and/or both parents had dependency to opium before and during pregnancy.
Materials and Methods: All experiments were carried out on Wistar rats. Opium dependency was induced by daily injections of opium (10 mg/kg/SC, bid/10 d) before mating. The presence of a vaginal plug was designated as gestation day. Treatment with opium continued through breeding and gestation until parturition. Spatial memory was tested in male offspring of control, saline and prenatal opium treated groups by a training trial and the probe test in the Morris water maze. Swimming escape latency in the maze and the ability to find the platform in the training trial were recorded. The time spent in the trigger zone and number of times the rats crossed the platform during the probe phase and swimming speed were measured.
Results:Thedata revealed increased escape latency and a greater distance traveled to find the hidden platform in the offspring’s whose mother, father and /or both parents were exposed to opium. Crossings to target quadrant at probe trials was significantly reduced in all of the prenatal opium exposed offsprings. The swimming speed showed a significant increase in father and parent’s opium exposed offspring. 
Conclusion:Prenatal opium exposure of either parent may cause deficits in spatial learning, but the precise mechanism(s) remain largely unknown.


1. Salmanzadeh F, Fathollahi Y, Semnanian S, Shafizadeh M. Dependence on morphine impairs the induction of long-term potentiation in the CA1 region of rat hippocampal slices. Brain Res 2003; 965:108-113.

2. Rimanoczy A,Vathy I. Prenatal exposure to morphine alters brain mu opioid receptor characteristics in rats. Brain Res 1995; 690:245-248.

3. Vathy I. Prenatal opiate exposure: long-term CNS consequences in the stress system of the offspring. Psychoneuroendocrinology 2002; 27:273-283.

4. Zarrindast MR, Eidi M, Eidi A,Oryan S. Effects of histamine and opioid systems on memory retention of passive avoidance learning in rats. Eur J Pharmacol 2002; 452:193-197.

5. 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; 186:72-77.

6. 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; 73:93-103.

7. Hutchings DE. Methadone and heroin during pregnancy: a review of behavioral effects in human and animal offspring. Neurobehav Toxicol Teratol 1982; 4:429-434.

8. Wilson GS. Clinical studies of infants and children exposed prenatally to heroin. Ann N Y Acad Sci 1989; 562:183-194.

9. Kalant H. Opium revisited: a brief review of its nature, composition, non-medical use and relative risks. Addiction 1997; 92:267-277.

10.  Katzung B, editor. Basic and Clinical Pharmacology 8th ed.  McGrow-Hill;2001.p.512.

11. Singer M. Drugs and development: the global impact of drug use and trafficking on social and economic development. Int J Drug Policy 2008; 19:467-478.

12. Hol T, Niesink M, Van Ree J M, Spruijt BM. Prenatal exposure to morphine affects juvenile play behavior and adult social behavior in rats. Pharmacol Biochem Behav 1996; 55:615-618.

13. Lavery S, Shah DK, Hunt RW, Filan PM, Doyle LW, Inder TE. Single versus bihemispheric amplitude-integrated electroencephalography in relation to cerebral injury and outcome in the term encephalopathic infant. J Paediatr Child Health 2008; 44:285-290.

14. Salmanzadeh F, Fathollahi Y, Semnanian S, Shafizadeh M, Kazemnejad A. Dependence on morphine leads to a prominent sharing among the different mechanisms of long-term potentiation in the CA1 region of rat hippocampus. Brain Res 2003; 963:93-100.

15. Davis CP, Franklin LM, Johnson GS, Schrott LM. Prenatal oxycodone exposure impairs spatial learning and/or memory in rats. Behav Brain Res 2010; 212:27-34.

16. Afarinesh MR, Sheibani V, Arabzadeh S, Shamsizadeh A. Effect of chronic morphine exposure on response properties of rat barrel cortex neurons. Addict Biol 2008; 13:31-39.

17. Eppolito AK, Smith RF. Long-term behavioral and developmental consequences of pre- and perinatal nicotine. Pharmacol Biochem Behav 2006; 85:835-841.

18. Abel EL. Paternal behavioral mutagenesis. Neurotoxicology 1989; 10:335-345.

19. Friedler G. Paternal exposures: impact on reproductive and developmental outcome. An overview. Pharmacol Biochem Behav  1996; 55:691-700.

20. Friedler G. Effects of limited paternal exposure to xenobiotic agents on the development of progeny. Neurobehav Toxicol Teratol 1985; 7:739-743.

21. Wang Y, Han T Z. Prenatal exposure to heroin in
mice elicits memory deficits that can be attributed to neuronal apoptosis. Neuroscience 2009; 160:330-338.

22. Nasiraei-Moghadam S, Kazeminezhad B, Dargahi L, Ahmadiani A. Maternal oral consumption of morphine increases Bax/Bcl-2 ratio and caspase 3 activity during early neural system development in rat embryos. J Mol Neurosci 2010; 41:156-164.

23. Bandstra E S, Morrow C E, Mansoor E,Accornero VH. Prenatal drug exposure: infant and toddler outcomes. J Addict Dis 2010; 29:245-258.

24.  Lin CS. Prenatal morphine alters the synaptic complex of postsynaptic density 95 with N-methyl-D-aspartate receptor subunit in hippocampal CA1 subregion of rat offspring leading to long-term cognitive deficits. Neuroscience 2009; 158:1326-1337.

25. Steingart RA, Barg J, Maslaton J, Nesher M,Yanai J. Pre- and postsynaptic alterations in the septohippocampal cholinergic innervations after prenatal exposure to drugs. Brain Res Bull 1998; 46:203-209.

26. Belcheva MM, Dawn S, Barg J, McHale RJ, Ho MT, Ignatova E, et al. Transient down-regulation of neonatal rat brain mu-opioid receptors upon in utero exposure to buprenorphine. Brain Res Dev Brain Res 1994; 80:158-162.

27. Hammer RP Jr, Seatriz JV,Ricalde a R. Regional dependence of morphine-induced mu-opiate receptor down-regulation in perinatal rat brain. Eur J Pharmacol 1991; 209:253-256.

28. Eriksson PS, Ronnback L. Effects of prenatal morphine treatment of rats on mortality, bodyweight and analgesic response in the offspring. Drug Alcohol Depend 1989; 24:187-194.

29. Lee B, Kwon S, Yeom M, Shim I, Lee H, Hahm D H. Wild ginseng attenuates repeated morphine-induced behavioral sensitization in rats. J Microbiol Biotechnol 2011; 21:757-765.