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Table of Contents
Vol. 31, No. 4, 2009
Issue release date: June 2009
Section title: Temperament
Editor's Choice -- Free Access
Dev Neurosci 2009;31:318–331
(DOI:10.1159/000216543)

The Meaning of Weaning: Influence of the Weaning Period on Behavioral Development in Mice

Curley J.P. · Jordan E.R. · Swaney W.T. · Izraelit A. · Kammel S. · Champagne F.A.
Department of Psychology, Columbia University, New York, N.Y., USA
email Corresponding Author

Abstract

Maternal care during the first week postpartum has long-term consequences for offspring development in rodents. However, mother-infant interactions continue well beyond this period, with several physiological and behavioral changes occurring between days 18 and 28 PN. In the present study, we investigate the long-term effects on offspring behavior of being weaned at day 21 PN versus day 28 PN. We found that male and female offspring engage in higher initial levels of social interaction if weaned at day 28 PN, as well as sexually dimorphic changes in exploratory behavior. Females who were themselves weaned earlier also appeared to wean their own pups earlier. Sex-specific effects of weaning age were found on levels of oxytocin and vasopressin V1a receptor density in the hypothalamus, central nucleus of the amygdala and nucleus accumbens. These results indicate that altering weaning age in mice may be a useful model for investigating the development of sexual dimorphism in neurobiology and behavior.

© 2009 S. Karger AG, Basel


  

Key Words

  • Weaning
  • Maternal care
  • Social behavior
  • Oxytocin
  • Vasopressin

References

  1. Adriani W, Laviola G (2002): Spontaneous novelty seeking and amphetamine-induced conditioning and sensitization in adult mice: evidence of dissociation as a function of age at weaning. Neuropsychopharmacology 27:225–236.
  2. Askew A, Gonzalez FA, Stahl JM, Karom MC (2006): Food competition and social experience effects on V1a receptor binding in the forebrain of male Long-Evans hooded rats. Horm Behav 49:328–336.
  3. Bale TL, Davis AM, Auger AP, Dorsa DM, McCarthy MM (2001): CNS region-specific oxytocin receptor expression: importance in regulation of anxiety and sex behavior. J Neurosci 21:2546–2552.
  4. Benus RF, Rondigs M (1996): Patterns of maternal effort in mouse lines bidirectionally selected for aggression. Anim Behav 51:67–75.
  5. Berman C (1990): Intergenerational transmission of maternal rejection rates among free-ranging rhesus monkeys on Cayo Santiago. Anim Behav 44:247–258.
  6. Bielsky IF, Hu SB, Szegda KL, Westphal H, Young LJ (2004): Profound impairment in social recognition and reduction in anxiety-like behavior in vasopressin V1a receptor knockout mice. Neuropsychopharmacology 29:483–493.
  7. Bielsky IF, Hu SB, Young LJ (2005): Sexual dimorphism in the vasopressin system: lack of an altered behavioral phenotype in female V1a receptor knockout mice. Behav Brain Res 164:132–136.
  8. Birke LI, Sadler D (1987): Differences in maternal behavior of rats and the sociosexual development of the offspring. Dev Psychobiol 20:85–99.
  9. Bosch OJ, Neumann ID (2008): Brain vasopressin is an important regulator of maternal behavior independent of dams’ trait anxiety. Proc Natl Acad Sci USA 105:17139–17144.
  10. Brunelli SA, Shindledecker RD, Hofer MA (1989): Early experience and maternal behavior in rats. Dev Psychobiol 22:295–314.
  11. Cameron N, Del Corpo A, Diorio J, McAllister K, Sharma S, Meaney MJ (2008a): Maternal programming of sexual behavior and hypothalamic-pituitary-gonadal function in the female rat. PLoS ONE 3:e2210.
  12. Cameron NM, Fish EW, Meaney MJ (2008b): Maternal influences on the sexual behavior and reproductive success of the female rat. Horm Behav 54:178–184.
  13. Champagne FA (2008): Epigenetic mechanisms and the transgenerational effects of maternal care. Front Neuroendocrinol 29:386–397.
  14. Champagne FA, Curley JP, Keverne EB, Bateson PP (2007): Natural variations in postpartum maternal care in inbred and outbred mice. Physiol Behav 91:325–334.
  15. Champagne F, Diorio J, Sharma S, Meaney MJ (2001): Naturally occurring variations in maternal behavior in the rat are associated with differences in estrogen-inducible central oxytocin receptors. Proc Natl Acad Sci USA 98:12736–12741.
  16. Champagne FA, Francis DD, Mar A, Meaney MJ (2003): Variations in maternal care in the rat as a mediating influence for the effects of environment on development. Physiol Behav 79:359–371.
  17. Champagne FA, Meaney MJ (2007): Transgenerational effects of social environment on variations in maternal care and behavioral response to novelty. Behav Neurosci 121:1353–1363.
  18. Champagne FA, Weaver IC, Diorio J, Dymov S, Szyf M, Meaney MJ (2006): Maternal care associated with methylation of the estrogen receptor-alpha1b promoter and estrogen receptor-alpha expression in the medial preoptic area of female offspring. Endocrinology 147:2909–2915.
  19. Cooper MA, Karom M, Huhman KL, Albers HE (2005): Repeated agonistic encounters in hamsters modulate AVP V1a receptor binding. Horm Behav 48:545–551.
  20. Counsilman JJ, Lim LM (1985): The definition of weaning. Anim Behav 32:1023–1024.

    External Resources

  21. Cushing BS, Kramer KM (2005): Mechanisms underlying epigenetic effects of early social experience: the role of neuropeptides and steroids. Neurosci Biobehav Rev 29:1089–1105.
  22. Devidze N, Mong JA, Jasnow AM, Kow LM, Pfaff DW (2005): Sex and estrogenic effects on coexpression of mRNAs in single ventromedial hypothalamic neurons. Proc Natl Acad Sci USA 102:14446–14451.
  23. Donaldson ZR, Young LJ (2008): Oxytocin, vasopressin, and the neurogenetics of sociality. Science 322:900–904.
  24. Dugger BN, Morris JA, Jordan CL, Breedlove SM (2007): Androgen receptors are required for full masculinization of the ventromedial hypothalamus (VMH) in rats. Horm Behav 51:195–201.
  25. Egashira N, Tanoue A, Matsuda T, Koushi E, Harada S, Takano Y, Tsujimoto G, Mishima K, Iwasaki K, Fujiwara M (2007): Impaired social interaction and reduced anxiety-related behavior in vasopressin V1a receptor knockout mice. Behav Brain Res 178:123–127.
  26. Fairbanks LA (1989): Early experience and cross-generational continuity of mother-infant contact in vervet monkeys. Dev Psychobiol 22:669–681.
  27. Fang J, Clemens LG (1999): Contextual determinants of female-female mounting in laboratory rats. Animal Behaviour 57:545–555.
  28. Ferdman N, Murmu RP, Bock J, Braun K, Leshem M (2007): Weaning age, social isolation, and gender, interact to determine adult explorative and social behavior, and dendritic and spine morphology in prefrontal cortex of rats. Behav Brain Res 180:174–182.
  29. File SE, Seth P (2003): A review of 25 years of the social interaction test. Eur J Pharmacol 463:35–53.
  30. Francis DD, Champagne FC, Meaney MJ (2000): Variations in maternal behaviour are associated with differences in oxytocin receptor levels in the rat. J Neuroendocrinol 12:1145–1148.
  31. Francis DD, Diorio J, Liu D, Meaney MJ (1999): Nongenomic transmission across generations of maternal behavior and stress responses in the rat. Science 286:1155–1158.
  32. Francis DD, Young LJ, Meaney MJ, Insel TR (2002): Naturally occurring differences in maternal care are associated with the expression of oxytocin and vasopressin (V1a) receptors: gender differences. J Neuroendocrinol 14:349–353.
  33. Harding SM, McGinnis MY (2004): Androgen receptor blockade in the MPOA or VMN: effects on male sociosexual behaviors. Physiol Behav 81:671–680.
  34. Ito A, Kikusui T, Takeuchi Y, Mori Y (2006): Effects of early weaning on anxiety and autonomic responses to stress in rats. Behav Brain Res 171:87–93.
  35. Iwata E, Kikusui T, Takeuchi Y, Mori Y (2007): Fostering and environmental enrichment ameliorate anxious behavior induced by early weaning in Balb/c mice. Physiol Behav 91:318–324.
  36. Janus K (1987): Early separation of young rats from the mother and the development of play fighting. Physiol Behav 39:471–476.
  37. Joffe JM, Levine S (1973): Effects of weaning age and adult handling on avoidance conditioning, open-field behavior, and plasma corticosterone of adult rats. Behav Biol 9:235–244.
  38. Kanari K, Kikusui T, Takeuchi Y, Mori Y (2005): Multidimensional structure of anxiety-related behavior in early-weaned rats. Behav Brain Res 156:45–52.
  39. Keverne EB, Curley JP (2004): Vasopressin, oxytocin and social behaviour. Curr Opin Neurobiol 14:777–783.
  40. Kikusui T, Isaka Y, Mori Y (2005): Early weaning deprives mouse pups of maternal care and decreases their maternal behavior in adulthood. Behav Brain Res 162:200–206.
  41. Kikusui T, Kiyokawa Y, Mori Y (2007): Deprivation of mother-pup interaction by early weaning alters myelin formation in male, but not female, ICR mice. Brain Res 1133:115–122.
  42. Kikusui T, Nakamura K, Kakuma Y, Mori Y (2006): Early weaning augments neuroendocrine stress responses in mice. Behav Brain Res 175:96–103.
  43. Kikusui T, Takeuchi Y, Mori Y (2004): Early weaning induces anxiety and aggression in adult mice. Physiol Behav 81:37–42.
  44. Kodama Y, Kikusui T, Takeuchi Y, Mori Y (2008): Effects of early weaning on anxiety and prefrontal cortical and hippocampal myelination in male and female Wistar rats. Dev Psychobiol 50:332–342.
  45. Konig B, Markl H (1987): Maternal care in house mice. I. The weaning strategy as a means for parental manipulation of offspring quality. Behav Ecol Sociobiol 20:1–9.
  46. Laviola G, Dell’Omo G (1997): Precocious weaning and changes in social variables during prepuberty affect cocaine reinforcing properties in adult mice. Psychobiology 25:163–170.
  47. Laviola G, Terranova ML (1998): The developmental psychobiology of behavioural plasticity in mice: the role of social experiences in the family unit. Neurosci Biobehav Rev 23:197–213.
  48. Lehmann J, Feldon J (2000): Long-term biobehavioral effects of maternal separation in the rat: consistent or confusing? Rev Neurosci 11:383–408.
  49. Lehmann J, Pryce CR, Bettschen D, Feldon J (1999): The maternal separation paradigm and adult emotionality and cognition in male and female Wistar rats. Pharmacol Biochem Behav 64:705–715.
  50. Lippmann M, Bress A, Nemeroff CB, Plotsky PM, Monteggia LM (2007): Long-term behavioural and molecular alterations associated with maternal separation in rats. Eur J Neurosci 25:3091–3098.
  51. Maestripieri D (2005): Early experience affects the intergenerational transmission of infant abuse in rhesus monkeys. Proc Natl Acad Sci USA 102:9726–9729.
  52. Martin P (1984): The meaning of weaning. Anim Behav 32:1257–1259.
  53. McCarthy MM, Kleopoulos SP, Mobbs CV, Pfaff DW (1994): Infusion of antisense oligodeoxynucleotides to the oxytocin receptor in the ventromedial hypothalamus reduces estrogen-induced sexual receptivity and oxytocin receptor binding in the female rat. Neuroendocrinology 59:432–440.
  54. Meaney MJ (2001): Maternal care, gene expression, and the transmission of individual differences in stress reactivity across generations. Annu Rev Neurosci 24:1161–1192.
  55. Miller L, Kramer R, Warner V, Wickramaratne P, Weissman M (1997): Intergenerational transmission of parental bonding among women. J Am Acad Child Adolesc Psychiatry 36:1134–1139.
  56. Moore CL (1984): Maternal contributions to the development of masculine sexual behavior in laboratory rats. Dev Psychobiol 17:347–356.
  57. Nakamura K, Kikusui T, Takeuchi Y, Mori Y (2003): The influence of early weaning on aggressive behavior in mice. J Vet Med Sci 65:1347–1349.
  58. Nakamura K, Kikusui T, Takeuchi Y, Mori Y (2008): Changes in social instigation- and food restriction-induced aggressive behaviors and hippocampal 5HT1B mRNA receptor expression in male mice from early weaning. Behav Brain Res 187:442–448.
  59. Nelson RJ, Trainor BC (2007): Neural mechanisms of aggression. Nat Rev Neurosci 8:536–546.
  60. Nephew BC, Bridges RS (2008): Central actions of arginine vasopressin and a V1a receptor antagonist on maternal aggression, maternal behavior, and grooming in lactating rats. Pharmacol Biochem Behav 91:77–83.
  61. Paxinos G, Franklin KBJ (2003): The Mouse Brain in Stereotaxic Coordinates. New York, Academic Press.
  62. Shimozuru M, Kodama Y, Iwasa T, Kikusui T, Takeuchi Y, Mori Y (2007): Early weaning decreases play-fighting behavior during the postweaning developmental period of Wistar rats. Dev Psychobiol 49:343–350.
  63. Skolnick NJ, Ackerman SH, Hofer MA, Weiner H (1980): Vertical transmission of acquired ulcer susceptibility in the rat. Science 208:1161–1163.
  64. Smith EFS (1991): Early social development in hooded rats (Rattus norvegicus): a link between weaning and play. Anim Behav 41:513–524.
  65. Sroufe LA (2005): Attachment and development: a prospective, longitudinal study from birth to adulthood. Attach Hum Dev 7:349–367.
  66. Terranova ML, Laviola G (1995): Individual differences in mouse behavioural development: effects of precocious weaning and ongoing sexual segregation. Anim Behav 50:1261–1271.

    External Resources

  67. Terranova ML, Laviola G (2001): Delta-opioid modulation of social interactions in juvenile mice weaned at different ages. Physiol Behav 73:393–400.
  68. Terranova ML, Laviola G, de Acetis L, Alleva E (1998): A description of the ontogeny of mouse agonistic behavior. J Comp Psychol 112:3–12.
  69. 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.
  70. Windle RJ, Gamble LE, Kershaw YM, Wood SA, Lightman SL, Ingram CD (2006): Gonadal steroid modulation of stress-induced hypothalamo-pituitary-adrenal activity and anxiety behavior: role of central oxytocin. Endocrinology 147:2423–2431.

  

Author Contacts

Dr. Frances A. Champagne
Department of Psychology, Columbia University
Room 406 Schermerhorn Hall, 1190 Amsterdam Avenue
New York, NY 10027 (USA)
Tel. +1 212 854 2589, Fax +1 212 854 3609, E-Mail fac2105@columbia.edu

  

Article Information

Received: December 15, 2008
Accepted: December 29, 2009
Published online: June 17, 2009
Number of Print Pages : 14
Number of Figures : 5, Number of Tables : 3, Number of References : 70

  

Publication Details

Developmental Neuroscience

Vol. 31, No. 4, Year 2009 (Cover Date: June 2009)

Journal Editor: Levison S.W. (Newark, N.J.)
ISSN: 0378-5866 (Print), eISSN: 1421-9859 (Online)

For additional information: http://www.karger.com/DNE


Copyright / Drug Dosage / Disclaimer

Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher or, in the case of photocopying, direct payment of a specified fee to the Copyright Clearance Center.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in goverment regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.

Abstract

Maternal care during the first week postpartum has long-term consequences for offspring development in rodents. However, mother-infant interactions continue well beyond this period, with several physiological and behavioral changes occurring between days 18 and 28 PN. In the present study, we investigate the long-term effects on offspring behavior of being weaned at day 21 PN versus day 28 PN. We found that male and female offspring engage in higher initial levels of social interaction if weaned at day 28 PN, as well as sexually dimorphic changes in exploratory behavior. Females who were themselves weaned earlier also appeared to wean their own pups earlier. Sex-specific effects of weaning age were found on levels of oxytocin and vasopressin V1a receptor density in the hypothalamus, central nucleus of the amygdala and nucleus accumbens. These results indicate that altering weaning age in mice may be a useful model for investigating the development of sexual dimorphism in neurobiology and behavior.

© 2009 S. Karger AG, Basel


  

Author Contacts

Dr. Frances A. Champagne
Department of Psychology, Columbia University
Room 406 Schermerhorn Hall, 1190 Amsterdam Avenue
New York, NY 10027 (USA)
Tel. +1 212 854 2589, Fax +1 212 854 3609, E-Mail fac2105@columbia.edu

  

Article Information

Received: December 15, 2008
Accepted: December 29, 2009
Published online: June 17, 2009
Number of Print Pages : 14
Number of Figures : 5, Number of Tables : 3, Number of References : 70

  

Publication Details

Developmental Neuroscience

Vol. 31, No. 4, Year 2009 (Cover Date: June 2009)

Journal Editor: Levison S.W. (Newark, N.J.)
ISSN: 0378-5866 (Print), eISSN: 1421-9859 (Online)

For additional information: http://www.karger.com/DNE


Article / Publication Details

First-Page Preview
Abstract of Temperament

Received: 12/15/2008
Accepted: 12/29/2009
Published online: 6/17/2009
Issue release date: June 2009

Number of Print Pages: 14
Number of Figures: 5
Number of Tables: 3

ISSN: 0378-5866 (Print)
eISSN: 1421-9859 (Online)

For additional information: http://www.karger.com/DNE


Copyright / Drug Dosage

Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher or, in the case of photocopying, direct payment of a specified fee to the Copyright Clearance Center.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in goverment regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.

References

  1. Adriani W, Laviola G (2002): Spontaneous novelty seeking and amphetamine-induced conditioning and sensitization in adult mice: evidence of dissociation as a function of age at weaning. Neuropsychopharmacology 27:225–236.
  2. Askew A, Gonzalez FA, Stahl JM, Karom MC (2006): Food competition and social experience effects on V1a receptor binding in the forebrain of male Long-Evans hooded rats. Horm Behav 49:328–336.
  3. Bale TL, Davis AM, Auger AP, Dorsa DM, McCarthy MM (2001): CNS region-specific oxytocin receptor expression: importance in regulation of anxiety and sex behavior. J Neurosci 21:2546–2552.
  4. Benus RF, Rondigs M (1996): Patterns of maternal effort in mouse lines bidirectionally selected for aggression. Anim Behav 51:67–75.
  5. Berman C (1990): Intergenerational transmission of maternal rejection rates among free-ranging rhesus monkeys on Cayo Santiago. Anim Behav 44:247–258.
  6. Bielsky IF, Hu SB, Szegda KL, Westphal H, Young LJ (2004): Profound impairment in social recognition and reduction in anxiety-like behavior in vasopressin V1a receptor knockout mice. Neuropsychopharmacology 29:483–493.
  7. Bielsky IF, Hu SB, Young LJ (2005): Sexual dimorphism in the vasopressin system: lack of an altered behavioral phenotype in female V1a receptor knockout mice. Behav Brain Res 164:132–136.
  8. Birke LI, Sadler D (1987): Differences in maternal behavior of rats and the sociosexual development of the offspring. Dev Psychobiol 20:85–99.
  9. Bosch OJ, Neumann ID (2008): Brain vasopressin is an important regulator of maternal behavior independent of dams’ trait anxiety. Proc Natl Acad Sci USA 105:17139–17144.
  10. Brunelli SA, Shindledecker RD, Hofer MA (1989): Early experience and maternal behavior in rats. Dev Psychobiol 22:295–314.
  11. Cameron N, Del Corpo A, Diorio J, McAllister K, Sharma S, Meaney MJ (2008a): Maternal programming of sexual behavior and hypothalamic-pituitary-gonadal function in the female rat. PLoS ONE 3:e2210.
  12. Cameron NM, Fish EW, Meaney MJ (2008b): Maternal influences on the sexual behavior and reproductive success of the female rat. Horm Behav 54:178–184.
  13. Champagne FA (2008): Epigenetic mechanisms and the transgenerational effects of maternal care. Front Neuroendocrinol 29:386–397.
  14. Champagne FA, Curley JP, Keverne EB, Bateson PP (2007): Natural variations in postpartum maternal care in inbred and outbred mice. Physiol Behav 91:325–334.
  15. Champagne F, Diorio J, Sharma S, Meaney MJ (2001): Naturally occurring variations in maternal behavior in the rat are associated with differences in estrogen-inducible central oxytocin receptors. Proc Natl Acad Sci USA 98:12736–12741.
  16. Champagne FA, Francis DD, Mar A, Meaney MJ (2003): Variations in maternal care in the rat as a mediating influence for the effects of environment on development. Physiol Behav 79:359–371.
  17. Champagne FA, Meaney MJ (2007): Transgenerational effects of social environment on variations in maternal care and behavioral response to novelty. Behav Neurosci 121:1353–1363.
  18. Champagne FA, Weaver IC, Diorio J, Dymov S, Szyf M, Meaney MJ (2006): Maternal care associated with methylation of the estrogen receptor-alpha1b promoter and estrogen receptor-alpha expression in the medial preoptic area of female offspring. Endocrinology 147:2909–2915.
  19. Cooper MA, Karom M, Huhman KL, Albers HE (2005): Repeated agonistic encounters in hamsters modulate AVP V1a receptor binding. Horm Behav 48:545–551.
  20. Counsilman JJ, Lim LM (1985): The definition of weaning. Anim Behav 32:1023–1024.

    External Resources

  21. Cushing BS, Kramer KM (2005): Mechanisms underlying epigenetic effects of early social experience: the role of neuropeptides and steroids. Neurosci Biobehav Rev 29:1089–1105.
  22. Devidze N, Mong JA, Jasnow AM, Kow LM, Pfaff DW (2005): Sex and estrogenic effects on coexpression of mRNAs in single ventromedial hypothalamic neurons. Proc Natl Acad Sci USA 102:14446–14451.
  23. Donaldson ZR, Young LJ (2008): Oxytocin, vasopressin, and the neurogenetics of sociality. Science 322:900–904.
  24. Dugger BN, Morris JA, Jordan CL, Breedlove SM (2007): Androgen receptors are required for full masculinization of the ventromedial hypothalamus (VMH) in rats. Horm Behav 51:195–201.
  25. Egashira N, Tanoue A, Matsuda T, Koushi E, Harada S, Takano Y, Tsujimoto G, Mishima K, Iwasaki K, Fujiwara M (2007): Impaired social interaction and reduced anxiety-related behavior in vasopressin V1a receptor knockout mice. Behav Brain Res 178:123–127.
  26. Fairbanks LA (1989): Early experience and cross-generational continuity of mother-infant contact in vervet monkeys. Dev Psychobiol 22:669–681.
  27. Fang J, Clemens LG (1999): Contextual determinants of female-female mounting in laboratory rats. Animal Behaviour 57:545–555.
  28. Ferdman N, Murmu RP, Bock J, Braun K, Leshem M (2007): Weaning age, social isolation, and gender, interact to determine adult explorative and social behavior, and dendritic and spine morphology in prefrontal cortex of rats. Behav Brain Res 180:174–182.
  29. File SE, Seth P (2003): A review of 25 years of the social interaction test. Eur J Pharmacol 463:35–53.
  30. Francis DD, Champagne FC, Meaney MJ (2000): Variations in maternal behaviour are associated with differences in oxytocin receptor levels in the rat. J Neuroendocrinol 12:1145–1148.
  31. Francis DD, Diorio J, Liu D, Meaney MJ (1999): Nongenomic transmission across generations of maternal behavior and stress responses in the rat. Science 286:1155–1158.
  32. Francis DD, Young LJ, Meaney MJ, Insel TR (2002): Naturally occurring differences in maternal care are associated with the expression of oxytocin and vasopressin (V1a) receptors: gender differences. J Neuroendocrinol 14:349–353.
  33. Harding SM, McGinnis MY (2004): Androgen receptor blockade in the MPOA or VMN: effects on male sociosexual behaviors. Physiol Behav 81:671–680.
  34. Ito A, Kikusui T, Takeuchi Y, Mori Y (2006): Effects of early weaning on anxiety and autonomic responses to stress in rats. Behav Brain Res 171:87–93.
  35. Iwata E, Kikusui T, Takeuchi Y, Mori Y (2007): Fostering and environmental enrichment ameliorate anxious behavior induced by early weaning in Balb/c mice. Physiol Behav 91:318–324.
  36. Janus K (1987): Early separation of young rats from the mother and the development of play fighting. Physiol Behav 39:471–476.
  37. Joffe JM, Levine S (1973): Effects of weaning age and adult handling on avoidance conditioning, open-field behavior, and plasma corticosterone of adult rats. Behav Biol 9:235–244.
  38. Kanari K, Kikusui T, Takeuchi Y, Mori Y (2005): Multidimensional structure of anxiety-related behavior in early-weaned rats. Behav Brain Res 156:45–52.
  39. Keverne EB, Curley JP (2004): Vasopressin, oxytocin and social behaviour. Curr Opin Neurobiol 14:777–783.
  40. Kikusui T, Isaka Y, Mori Y (2005): Early weaning deprives mouse pups of maternal care and decreases their maternal behavior in adulthood. Behav Brain Res 162:200–206.
  41. Kikusui T, Kiyokawa Y, Mori Y (2007): Deprivation of mother-pup interaction by early weaning alters myelin formation in male, but not female, ICR mice. Brain Res 1133:115–122.
  42. Kikusui T, Nakamura K, Kakuma Y, Mori Y (2006): Early weaning augments neuroendocrine stress responses in mice. Behav Brain Res 175:96–103.
  43. Kikusui T, Takeuchi Y, Mori Y (2004): Early weaning induces anxiety and aggression in adult mice. Physiol Behav 81:37–42.
  44. Kodama Y, Kikusui T, Takeuchi Y, Mori Y (2008): Effects of early weaning on anxiety and prefrontal cortical and hippocampal myelination in male and female Wistar rats. Dev Psychobiol 50:332–342.
  45. Konig B, Markl H (1987): Maternal care in house mice. I. The weaning strategy as a means for parental manipulation of offspring quality. Behav Ecol Sociobiol 20:1–9.
  46. Laviola G, Dell’Omo G (1997): Precocious weaning and changes in social variables during prepuberty affect cocaine reinforcing properties in adult mice. Psychobiology 25:163–170.
  47. Laviola G, Terranova ML (1998): The developmental psychobiology of behavioural plasticity in mice: the role of social experiences in the family unit. Neurosci Biobehav Rev 23:197–213.
  48. Lehmann J, Feldon J (2000): Long-term biobehavioral effects of maternal separation in the rat: consistent or confusing? Rev Neurosci 11:383–408.
  49. Lehmann J, Pryce CR, Bettschen D, Feldon J (1999): The maternal separation paradigm and adult emotionality and cognition in male and female Wistar rats. Pharmacol Biochem Behav 64:705–715.
  50. Lippmann M, Bress A, Nemeroff CB, Plotsky PM, Monteggia LM (2007): Long-term behavioural and molecular alterations associated with maternal separation in rats. Eur J Neurosci 25:3091–3098.
  51. Maestripieri D (2005): Early experience affects the intergenerational transmission of infant abuse in rhesus monkeys. Proc Natl Acad Sci USA 102:9726–9729.
  52. Martin P (1984): The meaning of weaning. Anim Behav 32:1257–1259.
  53. McCarthy MM, Kleopoulos SP, Mobbs CV, Pfaff DW (1994): Infusion of antisense oligodeoxynucleotides to the oxytocin receptor in the ventromedial hypothalamus reduces estrogen-induced sexual receptivity and oxytocin receptor binding in the female rat. Neuroendocrinology 59:432–440.
  54. Meaney MJ (2001): Maternal care, gene expression, and the transmission of individual differences in stress reactivity across generations. Annu Rev Neurosci 24:1161–1192.
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