Methamphetamine (MA) is one of the most abused psychostimulants in the Czech Republic and worldwide. Previous studies have demonstrated the adverse effects of maternal drug abuse. However, the father's contribution as a parent and donor of the half genetic information is unclear. The present study aimed to examine the effect of paternal MA exposure on behavioral development and locomotor activity in rat offspring. MA was administrated subcutaneously for 30 days at a dose of 5 mg/kg to adult male rats. The impact of paternal MA exposure on rat pups was investigated using behavioral tests during development and locomotor activity tests in adulthood. Prior to testing, adult offspring were exposed to an acute challenge dose of MA (1 mg/kg) to examine the possible sensitizing effect of the paternal treatment. Our results found no significant differences in behavioral development or locomotor activity in adulthood of offspring linked to paternal MA application. These results differ from the effects induced by maternal MA application. Further, our results demonstrated a significant increase in locomotor activity on the Laboras test after acute MA application. When comparing sex differences, females showed more activity than males in adulthood, whereas males were more active during development.

Department of Physiology 3rd Faculty of Medicine Charles University Prague Czech Republic

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ABEL EL. Paternal behavioral mutagenesis. Neurotoxicology. 1989;10:335–345. PubMed

ALTMAN J, SUDARSHAN K. Postnatal development of locomotion in the laboratory rat. Anim Behav. 1975;23:896–920. doi: 10.1016/0003-3472(75)90114-1. PubMed DOI

BECKER JB, ROBINSON TE, LORENZ KA. Sex difference and estrous cycle variations in amphetamine-elicited rotational behavior. Eur J Pharmacol. 1982;80:65–72. doi: 10.1016/0014-2999(82)90178-9. PubMed DOI

BECKER JB. Gender differences in dopaminergic function in striatum and nucleus accumbens. Pharmacol Biochem Behav. 1999;64:803–812. doi: 10.1016/s0091-3057(99)00168-9. PubMed DOI

BISAGNO V, FERGUSON D, LUINE VN. Chronic D-amphetamine induces sexually dimorphic effects on locomotion, recognition memory, and brain monoamines. Pharmacol Biochem Behav. 2003;74:859–867. doi: 10.1016/s0091-3057(03)00017-0. PubMed DOI

BUBENIKOVA-VALESOVA V, KACER P, SYSLOVA K, RAMBOUSEK L, JANOVSKY M, SCHUTOVA B, SLAMBEROVA R. Prenatal methamphetamine exposure affects the mesolimbic dopaminergic system and behavior in adult offspring. Int J Dev Neurosci. 2009;27:525–530. doi: 10.1016/j.ijdevneu.2009.06.012. PubMed DOI

COX BM, YOUNG AB, SEE RE, REICHEL CM. Sex differences in methamphetamine seeking in rats: Impact of oxytocin. Psychoneuroendocrinology. 2013;38:2343–2353. doi: 10.1016/j.psyneuen.2013.05.005. PubMed DOI PMC

DALTERIO S, STEGER R, MAYFIELD D, BARTKE A. Early cannabinoid exposure influences neuroendocrine and reproductive functions in mice: II. Postnatal effects. Pharmacol Biochem Behav. 1984;20:115–123. doi: 10.1016/0091-3057(84)90111-4. PubMed DOI

DATTEL BJ. Substance abuse in pregnancy. Semin Perinatol. 1990;14:179–187. PubMed

De CASTRO VL, DESTEFANI CR, DINIZ C, POLI P. Evaluation of neurodevelopmental effects on rats exposed prenatally to sulfentrazone. Neurotoxicology. 2007;28:1249–1259. doi: 10.1016/j.neuro.2007.06.001. PubMed DOI

DLUZEN DE, LIU B. Gender differences in methamphetamine use and responses: a review. Gend Med. 2008;5:24–35. doi: 10.1016/s1550-8579(08)80005-8. PubMed DOI

EUROPEAN MONITORING CENTRE FOR DRUGS AND DRUG ADDICTION. European drug report 2019: trends and developments. Office for Official Publications of the European Communities; 2019.

FISCHER DK, RICE RC, RIVERA AM, DONOHOE M, RAJADHYAKSHA AM. Altered reward sensitivity in female offspring of cocaine-exposed fathers. Behav Brain Res. 2017;332:23–31. doi: 10.1016/j.bbr.2017.05.054. PubMed DOI PMC

GEORGE VK, LI H, TELOKEN C, GRIGNON DJ, LAWRENCE WD, DHABUWALA CB. Effects of long-term cocaine exposure on spermatogenesis and fertility in peripubertal male rats. J Urol. 1996;155:327–331. PubMed

GLATT SJ, BOLAÑOS CA, TRKSAK GH, CROWDER-DUPONT C, JACKSON D. Prenatal cocaine exposure alters behavioral and neurochemical sensitization to amphetamine in adult rats. Neuropharmacology. 2000;39:599–610. doi: 10.1016/s0028-3908(99)00181-1. PubMed DOI

GOMEZ F, GARCÍA-GARCÍA L. Anxiogenic-like effects of fluoxetine render adult male rats vulnerable to the effects of a novel stress. Pharmacol Biochem Behav. 2017;153:32–44. doi: 10.1016/j.pbb.2016.12.007. PubMed DOI

HALL DA, STANIS JJ, AVILA HM, GULLEY JM. A comparison of amphetamine-and methamphetamine-induced locomotor activity in rats: evidence for qualitative differences in behavior. Psychopharmacology. 2008;195:469–478. doi: 10.1007/s00213-007-0923-8. PubMed DOI PMC

HE F, LIDOW IA, LIDOW MS. Consequences of paternal cocaine exposure in mice. Neurotoxicol Teratol. 2006;28:198–209. doi: 10.1016/j.ntt.2005.12.003. PubMed DOI

HOL T, Van den BERG CL, Van REE JM, SPRUIJT BM. Isolation during the play period in infancy decreases adult social interactions in rats. Behav Brain Res. 1999;100:91–97. doi: 10.1016/s0166-4328(98)00116-8. PubMed DOI

HRUBÁ L, SCHUTOVÁ B, ŠLAMBEROVÁ R, POMETLOVÁ M, ROKYTA R. Effect of methamphetamine exposure and cross-fostering on sensorimotor development of male and female rat pups. Dev Psychobiol. 2009;51:73–83. doi: 10.1002/dev.20346. PubMed DOI

HRUBÁ L, SCHUTOVÁ B, ŠLAMBEROVÁ R, POMETLOVÁ M. Does cross-fostering modify the impairing effect of methamphetamine on postnatal development of rat pups. Prague Med Rep. 2008;109:50–61. PubMed

HRUBÁ L, SCHUTOVÁ B, ŠLAMBEROVÁ R. Sex differences in anxiety-like behavior and locomotor activity following prenatal and postnatal methamphetamine exposure in adult rats. Physiol Behav. 2012;105:364–370. doi: 10.1016/j.physbeh.2011.08.016. PubMed DOI

KILLINGER CE, ROBINSON S, STANWOOD GD. Subtle biobehavioral effects produced by paternal cocaine exposure. Synapse. 2012;66:902–908. doi: 10.1002/syn.21582. PubMed DOI PMC

LAGASSE LL, WOULDES T, NEWMAN E, SMITH LM, SHAH RZ, DERAUF C, HUESTIS MA, ARRIA AM, DELLA GROTTA S, WILCOX T, LESTER BM. Prenatal methamphetamine exposure and neonatal neurobehavioral outcome in the USA and New Zealand. Neurotoxicol Teratol. 2011;33:166–175. doi: 10.1016/j.ntt.2010.06.009. PubMed DOI PMC

LAM MK, HOMEWOOD J, TAYLOR AJ, MAZURSKI EJ. Second generation effects of maternal alcohol consumption during pregnancy in rats. Prog Neuropsychopharmacol Biol Psychiatry. 2000;24:619–631. doi: 10.1016/s0278-5846(00)00097-x. PubMed DOI

LE Q, YAN B, YU X, LI Y, SONG H, ZHU H, HOU W, MA D, WU F, ZHOU Y, MA L. Drug-seeking motivation level in male rats determines offspring susceptibility or resistance to cocaine-seeking behaviour. Nat Commun. 2017;8:1–13. doi: 10.1038/ncomms15527. PubMed DOI PMC

LEDIG M, MISSLIN R, VOGEL E, HOLOWNIA A, COPIN JC, THOLEY G. Paternal alcohol exposure: developmental and behavioral effects on the offspring of rats. Neuropharmacology. 1998;37:57–66. doi: 10.1016/s0028-3908(97)00185-8. PubMed DOI

LEVIN ED, HAWKEY AB, HALL BJ, CAULEY M, SLADE S, YAZDANI E, KENOU B, WHITE H, WELLS C, REZVANI AH, MURPHY SK. Paternal THC exposure in rats causes long-lasting neurobehavioral effects in the offspring. Neurotoxicol Teratol. 74:2019. doi: 10.1016/j.ntt.2019.04.003. PubMed DOI

MACÚCHOVÁ E, NOHEJLOVÁ-DEYKUN K, ŠLAMBEROVÁ R. Effect of methamphetamine on cognitive functions of adult female rats prenatally exposed to the same drug. Physiol Res. 2013;62(Suppl 1):S89–S98. doi: 10.33549/physiolres.932598. PubMed DOI

MALINOVÁ-ŠEVČÍKOVÁ M, HREBÍČKOVÁ I, MACÚCHOVÁ E, NOVÁ E, POMETLOVÁ M, ŠLAMBEROVÁ R. Differences in maternal behavior and development of their pups depend on the time of methamphetamine exposure during gestation period. Physiol Res. 2014;63(Suppl 4):S559–S572. doi: 10.33549/physiolres.932925. PubMed DOI

MILESI-HALLÉ A, McMILLAN DE, LAURENZANA EM, BYRNES-BLAKE KA, OWENS SM. Sex differences in (+)-amphetamine-and (+)-methamphetamine-induced behavioral response in male and female Sprague-Dawley rats. Pharmacol Biochem Behav. 2007;86:140–149. doi: 10.1016/j.pbb.2006.12.018. PubMed DOI PMC

MURPHY MP, RICK JT, MILGRAM NW, IVY GO. A simple and rapid test of sensorimotor function in the aged rat. Neurobiol Learn Mem. 1995;64:181–186. doi: 10.1006/nlme.1995.1057. PubMed DOI

PALENICEK T, VOTAVA M, BUBENIKOVA V, HORACEK J. Increased sensitivity to the acute effects of MDMA (“ecstasy”) in female rats. Physiol Behav. 2005;86:546–553. doi: 10.1016/j.physbeh.2005.08.043. PubMed DOI

PELLIS SM, PELLIS VC. Development of righting when falling from a bipedal standing posture: evidence for the dissociation of dynamic and static righting reflexes in rats. Physiol Behav. 1994;56:659–663. doi: 10.1016/0031-9384(94)90223-2. PubMed DOI

RAMBOUSEK L, KACER P, SYSLOVA K, BUMBA J, BUBENIKOVA-VALESOVA V, SLAMBEROVA R. Sex differences in methamphetamine pharmacokinetics in adult rats and its transfer to pups through the placental membrane and breast milk. Drug Alcohol Depend. 2014;139:138–144. doi: 10.1016/j.drugalcdep.2014.03.023. PubMed DOI

REICHEL CM, CHAN CH, GHEE SM, SEE RE. Sex differences in escalation of methamphetamine self-administration: cognitive and motivational consequences in rats. Psychopharmacology (Berl) 2012;223:371–380. doi: 10.1007/s00213-012-2727-8. PubMed DOI PMC

SCHUTOVÁ B, HRUBÁ L, POMETLOVÁ M, DEYKUN K, ŠLAMBEROVÁ R. Cognitive functions and drug sensitivity in adult male rats prenatally exposed to methamphetamine. Physiol Res. 2009;58:741–750. doi: 10.33549/physiolres.931562. PubMed DOI

SCHUTOVÁ B, HRUBÁ L, POMETLOVÁ M, ROKYTA R, ŠLAMBEROVÁ R. Responsiveness to methamphetamine in adulthood is altered by prenatal exposure in rats. Physiol Behav. 2010;99:381–387. doi: 10.1016/j.physbeh.2009.12.004. PubMed DOI

SCHUTOVÁ B, HRUBÁ L, ROKYTA R, ŠLAMBEROVÁ R. Gender differences in behavioral changes elicited by prenatal methamphetamine exposure and application of the same drug in adulthood. Dev Psychobiol. 2013;55:232–242. doi: 10.1002/dev.21016. PubMed DOI

ŠEVČÍKOVÁ M, HREBÍČKOVÁ I, MACÚCHOVÁ E, ŠLAMBEROVÁ R. The influence of methamphetamine on maternal behavior and development of the pups during the neonatal period. Int J Dev Neurosci. 2017;59:37–46. doi: 10.1016/j.ijdevneu.2017.03.005. PubMed DOI

ŠEVČÍKOVÁ M, PETŘÍKOVÁ I, ŠLAMBEROVÁ R. Methamphetamine exposure during the first, but not the second half of prenatal development, affects social play behavior. Physiol Res. 2020;69:319–330. doi: 10.33549/physiolres.934230. PubMed DOI PMC

ŠLAMBEROVÁ R, CHAROUSOVÁ P, POMETLOVÁ M. Methamphetamine administration during gestation impairs maternal behavior. Dev Psychobiol. 2005;46:57–65. doi: 10.1002/dev.20042. PubMed DOI

ŠLAMBEROVÁ R, MACÚCHOVÁ E, NOHEJLOVÁ K, ŠTOFKOVÁ A, JURČOVIČOVÁ J. Effect of amphetamine on adult male and female rats prenatally exposed to methamphetamine. Prague Med Rep. 2014;115:43–59. doi: 10.14712/23362936.2014.5. PubMed DOI

ŠLAMBEROVÁ R, MIKULECKÁ A, POMETLOVÁ M, SCHUTOVÁ B, HRUBÁ L, DEYKUN K. Sex differences in social interaction of methamphetamine-treated rats. Behav Pharmacol. 2011;22:617–623. doi: 10.1097/FBP.0b013e32834afea4. PubMed DOI

ŠLAMBEROVÁ R, NOHEJLOVÁ K, OCHOZKOVÁ A, MIHALČÍKOVÁ L. What is the role of subcutaneous single injections on the behavior of adult male rats exposed to drugs? Physiol Res. 2018;67(Suppl 4):S665–S672. doi: 10.33549/physiolres.934053. PubMed DOI

ŠLAMBEROVÁ R, POMETLOVÁ M, CHAROUSOVÁ P. Postnatal development of rat pups is altered by prenatal methamphetamine exposure. Progress Neuropsychopharmacol Biol Psychiatry. 2006;30:82–88. doi: 10.1016/j.pnpbp.2005.06.006. PubMed DOI

ŠLAMBEROVÁ R, POMETLOVÁ M, ROKYTA R. Effect of methamphetamine exposure during prenatal and preweaning periods lasts for generations in rats. Dev Psychobiol. 2007;49:312–322. doi: 10.1002/dev.20203. PubMed DOI

ŠLAMBEROVÁ R, SCHUTOVÁ B, MATĚJOVSKÁ I, BERNÁŠKOVÁ K, ROKYTA R. Effects of a single postnatal methamphetamine administration on NMDA-induced seizures are sex-and prenatal exposure-specific. Naunyn Schmiedebergs Arch Pharmacol. 2009;380:109–114. doi: 10.1007/s00210-009-0427-7. PubMed DOI

SMITH LM, LAGASSE LL, DERAUF C, GRANT P, SHAH R, ARRIA A, HUESTIS M, HANING W, STRAUSS A, DELLA GROTTA S, FALLONE M, LIU J, LESTER BM. Prenatal methamphetamine use and neonatal neurobehavioral outcome. Neurotoxicol Teratol. 2008;30:20–28. doi: 10.1016/j.ntt.2007.09.005. PubMed DOI PMC

TURNER CD, BAGNARA JT. Biological effects of the ovarian hormones. Gen Endocrinol. 1976;6:466–476.

VERSTEGEN RH, WANG G, LANGENBERG-VERVERGAERT KP, REN LY, NULMAN I. Paternal exposure to recreational drugs before conception and its effect on live-born offspring: A scoping review. Birth Defects Res. 2020;112:970–988. doi: 10.1002/bdr2.1702. PubMed DOI

WHITE SL, VASSOLER FM, SCHMIDT HD, PIERCE RC, WIMMER ME. Enhanced anxiety in the male offspring of sires that self-administered cocaine. Addict Biol. 2016;21:802–810. doi: 10.1111/adb.12258. PubMed DOI PMC

An overview of the methamphetamine effect on male sexual behavior and reproductive system