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Altered locomotor and stereotyped responses to acute methamphetamine in adolescent, maternally separated rats

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Abstract

Rationale

Neonatal maternal separation (MS) has been used to model the effects of early life stress in rodents. MS alters behavioral responses to a variety of abused drugs, but few studies have examined its effects on methamphetamine sensitivity.

Objectives

We sought to determine the effects of MS on locomotor and stereotyped responses to low-to-moderate doses of methamphetamine in male and female adolescent rats.

Methods

Male and female rat pups were subjected to 3 h per day of MS on postnatal days (PN) 2–14 or a brief handling control procedure during the same period. During adolescence (approximately PN 40), all rats were tested for locomotor activity and stereotyped behavior in response to acute methamphetamine administration (0, 1.0, or 3.0 mg/kg, s.c.).

Results

MS rats of both sexes exhibited increased locomotor activity in a novel environment, relative to handled controls. MS increased the locomotor response to methamphetamine (METH), and this effect occurred at different doses for male (3.0 mg/kg) and female (1.0 mg/kg) rats. MS also increased stereotyped behavior in response to METH (1.0 mg/kg) in both sexes.

Conclusions

MS enhances the locomotor response to METH in a dose- and sex-dependent manner. These results suggest that individuals with a history of early life stress may be particularly vulnerable to the psychostimulant effects of METH, even at relatively low doses.

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References

  • Arborelius L, Eklund MB (2007) Both long and brief maternal separation produce persistent changes in tissue levels of brain monoamines in middle-aged female rats. Neuroscience 145(2):738–750

    Article  PubMed  CAS  Google Scholar 

  • Bolanos CA, Glatt SJ, Jackson D (1998) Subsensitivity to dopaminergic drugs in periadolescent rats: a behavioral and neurochemical analysis. Brain Res Dev Brain Res 111(1):25–33

    Article  PubMed  CAS  Google Scholar 

  • Brake WG, Zhang TY, Diorio J, Meaney MJ, Gratton A (2004) Influence of early postnatal rearing conditions on mesocorticolimbic dopamine and behavioural responses to psychostimulants and stressors in adult rats. Eur J Neurosci 19(7):1863–1874

    Article  PubMed  Google Scholar 

  • Brecht ML, O'Brien A, von Mayrhauser C, Anglin MD (2004) Methamphetamine use behaviors and gender differences. Addict Behav 29(1):89–106

    Article  PubMed  Google Scholar 

  • Creese I, Iversen SD (1974) The role of forebrain dopamine systems in amphetamine induced stereotyped behavior in the rat. Psychopharmacologia 39(4):345–357

    Article  PubMed  CAS  Google Scholar 

  • Daniels WM, Pietersen CY, Carstens ME, Stein DJ (2004) Maternal separation in rats leads to anxiety-like behavior and a blunted ACTH response and altered neurotransmitter levels in response to a subsequent stressor. Metab Brain Dis 19(1):3–14

    Article  PubMed  CAS  Google Scholar 

  • Desbonnet L, Garrett L, Daly E, McDermott KW, Dinan TG (2008) Sexually dimorphic effects of maternal separation stress on corticotrophin-releasing factor and vasopressin systems in the adult rat brain. Int J Dev Neurosci 26(3–4):259–268

    Article  PubMed  CAS  Google Scholar 

  • Dluzen DE, Liu B (2008) Gender differences in methamphetamine use and responses: a review. Gend Med 5(1):24–35

    Article  PubMed  Google Scholar 

  • Dube SR, Cook M, Edwards VJ (2010) Health-related outcomes of adverse childhood experiences in Texas, 2002. Prev Chron Dis 7(3):1–9

    Google Scholar 

  • Faure J, Stein DJ, Daniels W (2009) Maternal separation fails to render animals more susceptible to methamphetamine-induced conditioned place preference. Metab Brain Dis 24(4):541–559

    Article  PubMed  CAS  Google Scholar 

  • Festa ED, Russo SJ, Gazi FM, Niyomchai T, Kemen LM, Lin SN, Foltz R, Jenab S, Quinones-Jenab V (2004) Sex differences in cocaine-induced behavioral responses, pharmacokinetics, and monoamine levels. Neuropharmacology 46(5):672–687

    Article  PubMed  CAS  Google Scholar 

  • Hall FS, Wilkinson LS, Humby T, Robbins TW (1999) Maternal deprivation of neonatal rats produces enduring changes in dopamine function. Synapse 32(1):37–43

    Article  PubMed  CAS  Google Scholar 

  • Hensleigh E, Smedley L, Pritchard LM (2011) Sex, but not repeated maternal separation during the first postnatal week, influences novel object exploration and amphetamine sensitivity. Dev Psychobiol 53(2):132–140. doi:10.1002/dev.20499

    Article  PubMed  CAS  Google Scholar 

  • Huot RL, Thrivikraman KV, Meaney MJ, Plotsky PM (2001) Development of adult ethanol preference and anxiety as a consequence of neonatal maternal separation in Long Evans rats and reversal with antidepressant treatment. Psychopharmacology (Berl) 158(4):366–373

    Article  CAS  Google Scholar 

  • Institute for Laboratory Animal Research (1996) Guide for the care and use of laboratory animals. National Academy Press, Washington D.C

    Google Scholar 

  • Levine S (2001) Primary social relationships influence the development of the hypothalamic–pituitary–adrenal axis in the rat. Physiol Behav 73(3):255–260

    Article  PubMed  CAS  Google Scholar 

  • Li Y, Robinson TE, Bhatnagar S (2003) Effects of maternal separation on behavioural sensitization produced by repeated cocaine administration in adulthood. Brain Res 960(1–2):42–47

    Article  PubMed  CAS  Google Scholar 

  • Marin MT, Planeta CS (2004) Maternal separation affects cocaine-induced locomotion and response to novelty in adolescent, but not in adult rats. Brain Res 1013(1):83–90

    Article  PubMed  CAS  Google Scholar 

  • Marmendal M, Roman E, Eriksson CJ, Nylander I, Fahlke C (2004) Maternal separation alters maternal care, but has minor effects on behavior and brain opioid peptides in adult offspring. Dev Psychobiol 45(3):140–152

    Article  PubMed  CAS  Google Scholar 

  • Matthews K, Hall FS, Wilkinson LS, Robbins TW (1996) Retarded acquisition and reduced expression of conditioned locomotor activity in adult rats following repeated early maternal separation: effects of prefeeding, d-amphetamine, dopamine antagonists and clonidine. Psychopharmacology (Berl) 126(1):75–84

    Article  CAS  Google Scholar 

  • Matthews K, Robbins TW, Everitt BJ, Caine SB (1999) Repeated neonatal maternal separation alters intravenous cocaine self-administration in adult rats. Psychopharmacology (Berl) 141(2):123–134

    Article  CAS  Google Scholar 

  • Matthews K, Dalley JW, Matthews C, Tsai TH, Robbins TW (2001) Periodic maternal separation of neonatal rats produces region- and gender-specific effects on biogenic amine content in postmortem adult brain. Synapse 40(1):1–10

    Article  PubMed  CAS  Google Scholar 

  • Meaney MJ, Brake W, Gratton A (2002) Environmental regulation of the development of mesolimbic dopamine systems: a neurobiological mechanism for vulnerability to drug abuse? Psychoneuroendocrinology 27(1–2):127–138

    Article  PubMed  CAS  Google Scholar 

  • Messina N, Marinelli-Casey P, Hillhouse M, Rawson R, Hunter J, Ang A (2008) Childhood adverse events and methamphetamine use among men and women. J Psychoact Drugs S5:399–409

    Article  Google Scholar 

  • Milesi-Halle A, Hendrickson HP, Laurenzana EM, Gentry WB, Owens SM (2005) Sex- and dose-dependency in the pharmacokinetics and pharmacodynamics of (+)-methamphetamine and its metabolite (+)-amphetamine in rats. Toxicol Appl Pharmacol 209(3):203–213

    Article  PubMed  CAS  Google Scholar 

  • Moffett MC, Vicentic A, Kozel M, Plotsky P, Francis DD, Kuhar MJ (2007) Maternal separation alters drug intake patterns in adulthood in rats. Biochem Pharmacol 73(3):321–330

    Article  PubMed  CAS  Google Scholar 

  • Muhammad A, Kolb B (2011) Maternal separation altered behavior and neuronal spine density without influencing amphetamine sensitization. Behav Brain Res 223(1):7–16

    Article  PubMed  CAS  Google Scholar 

  • Pihoker C, Owens MJ, Kuhn CM, Schanberg SM, Nemeroff CB (1993) Maternal separation in neonatal rats elicits activation of the hypothalamic–pituitary–adrenocortical axis: a putative role for corticotropin-releasing factor. Psychoneuroendocrinology 18(7):485–493

    Article  PubMed  CAS  Google Scholar 

  • Planeta CS, Marin MT (2002) Effect of cocaine on periadolescent rats with or without early maternal separation. Braz J Med Biol Res 35(11):1367–1371

    Article  PubMed  CAS  Google Scholar 

  • Ploj K, Roman E, Nylander I (2003) Long-term effects of maternal separation on ethanol intake and brain opioid and dopamine receptors in male Wistar rats. Neurosci 121(3):787–799

    Article  CAS  Google Scholar 

  • Plotsky PM, Meaney MJ (1993) Early, postnatal experience alters hypothalamic corticotropin-releasing factor (CRF) mRNA, median eminence CRF content and stress-induced release in adult rats. Mol Brain Res 18(3):195–200

    Article  PubMed  CAS  Google Scholar 

  • Rosenfeld P, Wetmore JB, Levine S (1992) Effects of repeated maternal separations on the adrenocortical response to stress of preweanling rats. Physiol Behav 52(4):787–791

    Article  PubMed  CAS  Google Scholar 

  • Sapolsky RM, Meaney MJ (1986) Maturation of the adrenocortical stress response: neuroendocrine control mechanisms and the stress hyporesponsive period. Brain Res 396(1):64–76

    Article  PubMed  CAS  Google Scholar 

  • Schindler CW, Bross JG, Thorndike EB (2005) Gender differences in the behavioral effects of methamphetamine. Eur J Pharmacol 442(3):231–235

    Article  Google Scholar 

  • Shoblock JR, Sullivan EB, Maisonneuve IM, Glick SD (2003) Neurochemical and behavioral differences between d-methamphetamine and d-amphetamine in rats. Psychopharmacology (Berl) 165(4):359–369

    CAS  Google Scholar 

  • Sinha R (2008) Chronic stress, drug use, and vulnerability to addiction. Ann NY Acad Sci 1141:105–130

    Article  PubMed  CAS  Google Scholar 

  • Stanton ME, Wallstrom J, Levine S (1987) Maternal contact inhibits pituitary-adrenal stress responses in preweanling rats. Dev Psychobiol 20(2):131–145

    Article  PubMed  CAS  Google Scholar 

  • Troakes C, Ingram CD (2009) Anxiety behaviour of the male rat on the elevated plus maze: associated regional increase in c-fos mRNA expression and modulation by early maternal separation. Stress 12(4):362–369

    Article  PubMed  CAS  Google Scholar 

  • Walker QD, Morris SE, Arrant AE, Nagel JM, Parylak S, Zhou G, Caster JM, Kuhn CM (2010) Dopamine uptake inhibitors but not dopamine releasers induce greater increases in motor behavior and extracellular dopamine in adolescent rats than in adult male rats. J Pharmacol Exp Ther 335(1):124–132

    Article  PubMed  CAS  Google Scholar 

  • Wobbrock JO, Findlater L, Gergle D, Higgins JJ (2011) The aligned rank transform for nonparametric factorial analyses using only ANOVA procedures. Conf Hum Factors Comput Syst-Proc 143–146

  • Zorrilla EP (1997) Multiparous species present problems (and possibilities) to developmentalists. Dev Psychobiol 30(2):141–150

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgments

This work was supported by grants from the National Center for Research Resources (5P20RR016464-11) and the National Institute of General Medical Sciences (8 P20 GM103440-11) of the National Institutes of Health. We would like to thank Kelly AbuAli and Alan Jager for their assistance with editing and scoring behavioral videos. The experiments described herein comply with the Public Health Service Policy on Humane Care and Use of Laboratory Animals.

Conflict of interest

The authors declare that they have no conflicts of interest.

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Authors and Affiliations

  1. Department of Psychology, University of Nevada Las Vegas, 4505 Maryland Parkway, Las Vegas, NV, 89154-5030, USA

    Laurel M. Pritchard, Emily Hensleigh & Sarah Lynch

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  1. Laurel M. Pritchard
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  2. Emily Hensleigh
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  3. Sarah Lynch
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Correspondence to Laurel M. Pritchard.

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Pritchard, L.M., Hensleigh, E. & Lynch, S. Altered locomotor and stereotyped responses to acute methamphetamine in adolescent, maternally separated rats. Psychopharmacology 223, 27–35 (2012). https://doi.org/10.1007/s00213-012-2679-z

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  • DOI: https://doi.org/10.1007/s00213-012-2679-z

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