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Effects of early postnatal sibling deprivation on anxiety and vulnerability to cocaine in offspring rats

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Abstract

Rationale

Early-life experience has long-term consequences on affective behavior and drug abuse in adults. While many manipulations used to study these consequences alter mother–infant interactions, the effects of sibling interactions are less well characterized.

Objectives

To examine the long-term effects of early postnatal sibling deprivation (EPSD) on anxiety-like behavior, sucrose preference and behavioral responses to cocaine in adult rats.

Materials and methods

After EPSD manipulation, in which litters were culled to one pup on postnatal day 1 (PN1) or 7 (PN7), the dams’ maternal behavior was observed. After the pups reached adulthood, we tested their behavioral responses in the elevated plus maze and sucrose consumption, and to cocaine conditioned place preference and cocaine sensitization.

Results

The pups with EPSD on PN1 received more maternal licking/grooming during the first postnatal week. EPSD on PN1 but not PN7 enhanced locomotor activity in the open field test and exploration of open arms in the elevated plus maze in both female and male offspring. While EPSD had no effect on sucrose intake in adult rats, it decreased vulnerability to cocaine sensitization and cocaine conditioned place preference in male but not female rats.

Conclusion

Our findings that early postnatal sibling deprivation influences maternal licking/grooming behavior, as well as anxiety-like behavior and vulnerability to drugs in pups that have grown to adulthood, suggests that both sibling interaction and maternal behavior, play critical roles in individual development.

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References

  • Anisman H, Zaharia MD, Meaney MJ, Merali Z (1998) Do early-life events permanently alter behavioral and hormonal responses to stressors? Int J Dev Neurosci 16:149–164

    Article  PubMed  CAS  Google Scholar 

  • Bennett JC, McRae PA, Levy LJ, Frick KM (2006) Long-term continuous, but not daily, environmental enrichment reduces spatial memory decline in aged male mice. Neurobiol Learn Mem 85:139–152

    Article  PubMed  Google Scholar 

  • Boccia ML, Pedersen CA (2001) Brief vs. long maternal separations in infancy: contrasting relationships with adult maternal behavior and lactation levels of aggression and anxiety. Psychoneuroendocrinology 26:657–672

    Article  PubMed  CAS  Google Scholar 

  • Borowsky B, Kuhn CM (1991) Chronic cocaine administration sensitizes behavioral but not neuroendocrine responses. Brain Res 543:301–306

    Article  PubMed  CAS  Google Scholar 

  • Boudreau AC, Wolf ME (2005) Behavioral sensitization to cocaine is associated with increased AMPA receptor surface expression in the nucleus accumbens. J Neurosci 25:9144–9151

    Article  PubMed  CAS  Google Scholar 

  • Bredy TW, Lee AW, Meaney MJ, Brown RE (2004) Effect of neonatal handling and paternal care on offspring cognitive development in the monogamous California mouse (Peromyscus californicus). Horm Behav 46:30–38

    Article  PubMed  Google Scholar 

  • Caldji C, Tannenbaum B, Sharma S, Francis D, Plotsky PM, Meaney MJ (1998) Maternal care during infancy regulates the development of neural systems mediating the expression of fearfulness in the rat. Proc Natl Acad Sci U S A 95:5335–5340

    Article  PubMed  CAS  Google Scholar 

  • Choi S, DiSilvio B, Unangst J, Fernstrom JD (2007) Effect of chronic infusion of olanzapine and clozapine on food intake and body weight gain in male and female rats. Life Sci 81:1024–1030

    Article  PubMed  CAS  Google Scholar 

  • Cukor D, McGinn LK (2006) History of child abuse and severity of adult depression: the mediating role of cognitive schema. J Child Sex Abus 15:19–34

    Article  PubMed  Google Scholar 

  • Dackis CA, Kampman KM, Lynch KG, Pettinati HM, O'Brien CP (2005) A double-blind, placebo-controlled trial of modafinil for cocaine dependence. Neuropsychopharmacology 30:205–211

    Article  PubMed  CAS  Google Scholar 

  • Durand M, Sarrieau A, Aguerre S, Mormede P, Chaouloff F (1998) Differential effects of neonatal handling on anxiety, corticosterone response to stress, and hippocampal glucocorticoid and serotonin (5-HT)2A receptors in Lewis rats. Psychoneuroendocrinology 23:323–335

    Article  PubMed  CAS  Google Scholar 

  • Eklund MB, Arborelius L (2006) Twice daily long maternal separations in Wistar rats decreases anxiety-like behaviour in females but does not affect males. Behav Brain Res 172:278–285

    Article  PubMed  Google Scholar 

  • Henniger MS, Spanagel R, Wigger A, Landgraf R, Holter SM (2002) Alcohol self-administration in two rat lines selectively bred for extremes in anxiety-related behavior. Neuropsychopharmacology 26:729–736

    Article  PubMed  CAS  Google Scholar 

  • Howe MG, Madgett ME (1975) Mental health problems associated with the only child. Can Psychiatr Assoc J 20:189–194

    PubMed  CAS  Google Scholar 

  • Huot RL, Plotsky PM, Lenox RH, McNamara RK (2002) Neonatal maternal separation reduces hippocampal mossy fiber density in adult Long Evans rats. Brain Res 950:52–63

    Article  PubMed  CAS  Google Scholar 

  • Jaworski JN, Francis DD, Brommer CL, Morgan ET, Kuhar MJ (2005) Effects of early maternal separation on ethanol intake, GABA receptors and metabolizing enzymes in adult rats. Psychopharmacology (Berl) 181:8–15

    Article  CAS  Google Scholar 

  • Kelly JP, Leonard BE (1999) An investigation of the antidepressant properties of lofepramine and its desmethylated metabolites in the forced swim and olfactory bulbectomized rat models of depression. Eur Neuropsychopharmacol 9:101–105

    Article  PubMed  CAS  Google Scholar 

  • Kemppainen L, Jokelainen J, Jarvelin MR, Isohanni M, Rasanen P (2001) The one-child family and violent criminality: a 31-year follow-up study of the Northern Finland 1966 Birth Cohort. Am J Psychiatry 158:960–962

    PubMed  CAS  Google Scholar 

  • Kosten TA, Miserendino MJ, Kehoe P (2000) Enhanced acquisition of cocaine self-administration in adult rats with neonatal isolation stress experience. Brain Res 875:44–50

    Article  PubMed  CAS  Google Scholar 

  • Kosten TA, Sanchez H, Zhang XY, Kehoe P (2004) Neonatal isolation enhances acquisition of cocaine self-administration and food responding in female rats. Behav Brain Res 151:137–149

    Article  PubMed  CAS  Google Scholar 

  • Kosten T, Kosten T, Poling J, Oliveto A (2005) “Incubation” of cocaine relapse during a disulfiram clinical trial. CPDD. Annual Meeting Abstracts, p 90

  • Kosten TA, Zhang XY, Kehoe P (2006) Heightened cocaine and food self-administration in female rats with neonatal isolation experience. Neuropsychopharmacology 31:70–76

    Article  PubMed  CAS  Google Scholar 

  • Laviola G, Dell'Omo G, Alleva E, Bignami G (1992) Ontogeny of cocaine hyperactivity and conditioned place preference in mice. Psychopharmacology (Berl) 107:221–228

    Article  CAS  Google Scholar 

  • Lehmann J, Stohr T, Feldon J (2000) Long-term effects of prenatal stress experiences and postnatal maternal separation on emotionality and attentional processes. Behav Brain Res 107:133–144

    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 960:42–47

    Article  PubMed  CAS  Google Scholar 

  • Li YQ, Wang XY, Zhai HF, Zhang XY, Kosten T, Lu L (2008) Sex- and age-dependent effects of early postnatal sibling deprivation on spatial learning and memory in adult rats. Behav Brain Res 186:138–142

    Article  PubMed  Google Scholar 

  • Liu D, Diorio J, Day JC, Francis DD, Meaney MJ (2000) Maternal care, hippocampal synaptogenesis and cognitive development in rats. Nat Neurosci 3:799–806

    Article  PubMed  CAS  Google Scholar 

  • Lu L, Ceng X, Huang M (2000) Corticotropin-releasing factor receptor type I mediates stress-induced relapse to opiate dependence in rats. Neuroreport 11:2373–2378

    Article  PubMed  CAS  Google Scholar 

  • Lu L, Liu Z, Huang M, Zhang Z (2003) Dopamine-dependent responses to cocaine depend on corticotropin-releasing factor receptor subtypes. J Neurochem 84:1378–1386

    Article  PubMed  CAS  Google Scholar 

  • Macri S, Mason GJ, Wurbel H (2004) Dissociation in the effects of neonatal maternal separations on maternal care and the offspring's HPA and fear responses in rats. Eur J Neurosci 20:1017–1024

    Article  PubMed  Google Scholar 

  • Maldonado AM, Kirstein CL (2005) Handling alters cocaine-induced activity in adolescent but not adult male rats. Physiol Behav 84:321–326

    Article  PubMed  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) 141:123–134

    Article  CAS  Google Scholar 

  • McEwen BS (2003) Early life influences on life-long patterns of behavior and health. Ment Retard Dev Disabil Res Rev 9:149–154

    Article  PubMed  Google Scholar 

  • Meaney MJ, Szyf M (2005) Maternal care as a model for experience-dependent chromatin plasticity? Trends Neurosci 28:456–463

    Article  PubMed  CAS  Google Scholar 

  • Meaney MJ, Aitken DH, van Berkel C, Bhatnagar S, Sapolsky RM (1988) Effect of neonatal handling on age-related impairments associated with the hippocampus. Science 239:766–768

    Article  PubMed  CAS  Google Scholar 

  • Meaney MJ, Aitken DH, Bhatnagar S, Sapolsky RM (1991) Postnatal handling attenuates certain neuroendocrine, anatomical, and cognitive dysfunctions associated with aging in female rats. Neurobiol Aging 12:31–38

    Article  PubMed  CAS  Google Scholar 

  • Melo AI, Lovic V, Gonzalez A, Madden M, Sinopoli K, Fleming AS (2006) Maternal and littermate deprivation disrupts maternal behavior and social-learning of food preference in adulthood: tactile stimulation, nest odor, and social rearing prevent these effects. Dev Psychobiol 48:209–219

    Article  PubMed  Google Scholar 

  • Merali Z, McIntosh J, Kent P, Michaud D, Anisman H (1998) Aversive and appetitive events evoke the release of corticotropin-releasing hormone and bombesin-like peptides at the central nucleus of the amygdala. J Neurosci 18:4758–4766

    PubMed  CAS  Google Scholar 

  • Moffett MC, Harley J, Francis D, Sanghani SP, Davis WI, Kuhar MJ (2006) Maternal separation and handling affects cocaine self-administration in both the treated pups as adults and the dams. J Pharmacol Exp Ther 317:1210–1218

    Article  PubMed  CAS  Google Scholar 

  • Oitzl MS, Workel JO, Fluttert M, Frosch F, De Kloet ER (2000) Maternal deprivation affects behaviour from youth to senescence: amplification of individual differences in spatial learning and memory in senescent Brown Norway rats. Eur J Neurosci 12:3771–3780

    Article  PubMed  CAS  Google Scholar 

  • Penke Z, Felszeghy K, Fernette B, Sage D, Nyakas C, Burlet A (2001) Postnatal maternal deprivation produces long-lasting modifications of the stress response, feeding and stress-related behaviour in the rat. Eur J Neurosci 14:747–755

    Article  PubMed  CAS  Google Scholar 

  • Renard GM, Suarez MM, Levin GM, Rivarola MA (2005) Sex differences in rats: effects of chronic stress on sympathetic system and anxiety. Physiol Behav 85:363–369

    Article  PubMed  CAS  Google Scholar 

  • Richardson NR, Roberts DC (1996) Progressive ratio schedules in drug self-administration studies in rats: a method to evaluate reinforcing efficacy. J Neurosci Methods 66:1–11

    Article  PubMed  CAS  Google Scholar 

  • Romeo RD, Mueller A, Sisti HM, Ogawa S, McEwen BS, Brake WG (2003) Anxiety and fear behaviors in adult male and female C57BL/6 mice are modulated by maternal separation. Horm Behav 43:561–567

    Article  PubMed  Google Scholar 

  • Sinha R, Kimmerling A, Doebrick C, Kosten TR (2007) Effects of lofexidine on stress-induced and cue-induced opioid craving and opioid abstinence rates: preliminary findings. Psychopharmacology (Berl) 190:569–574

    Article  CAS  Google Scholar 

  • Slotten HA, Kalinichev M, Hagan JJ, Marsden CA, Fone KC (2006) Long-lasting changes in behavioural and neuroendocrine indices in the rat following neonatal maternal separation: gender-dependent effects. Brain Res 1097:123–132

    Article  PubMed  CAS  Google Scholar 

  • Sobrian SK, Marr L, Ressman K (2003) Prenatal cocaine and/or nicotine exposure produces depression and anxiety in aging rats. Prog Neuropsychopharmacol Biol Psychiatry 27:501–518

    Article  PubMed  CAS  Google Scholar 

  • Tseng WS, Kuotai T, Hsu J, Chiu JH, Yu L, Kameoka V (1988) Family planning and child mental health in China: the Nanjing Survey. Am J Psychiatry 145:1396–1403

    PubMed  CAS  Google Scholar 

  • Walker MP, Brakefield T, Hobson JA, Stickgold R (2003) Dissociable stages of human memory consolidation and reconsolidation. Nature 425:616–620

    Article  PubMed  CAS  Google Scholar 

  • Wang J, Fang Q, Liu Z, Lu L (2006) Region-specific effects of brain corticotropin-releasing factor receptor type 1 blockade on footshock-stress- or drug-priming-induced reinstatement of morphine conditioned place preference in rats. Psychopharmacology (Berl) 185:19–28

    Article  CAS  Google Scholar 

  • Weaver IC, Cervoni N, Champagne FA, D'Alessio AC, Sharma S, Seckl JR, Dymov S, Szyf M, Meaney MJ (2004) Epigenetic programming by maternal behavior. Nat Neurosci 7:847–854

    Article  PubMed  CAS  Google Scholar 

  • Wigger A, Neumann ID (1999) Periodic maternal deprivation induces gender-dependent alterations in behavioral and neuroendocrine responses to emotional stress in adult rats. Physiol Behav 66:293–302

    Article  PubMed  CAS  Google Scholar 

  • Zhang XY, Sanchez H, Kehoe P, Kosten TA (2005) Neonatal isolation enhances maintenance but not reinstatement of cocaine self-administration in adult male rats. Psychopharmacology (Berl) 177:391–399

    Article  CAS  Google Scholar 

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Acknowledgments

This work was supported in part by the National Basic Research Program of China (No: 2007CB512302 and 2003CB 515400), the National High Technology Research and Development Program of China (863 Program, 2006AA02Z4D1) and the Natural Science Foundation of China (No: 30570576, 30670713 and 30725016).

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Correspondence to Lin Lu.

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Li, YQ., Wang, XY., Zhai, Hf. et al. Effects of early postnatal sibling deprivation on anxiety and vulnerability to cocaine in offspring rats. Psychopharmacology 199, 245–253 (2008). https://doi.org/10.1007/s00213-008-1169-9

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  • DOI: https://doi.org/10.1007/s00213-008-1169-9

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