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Proceedings of the National Academy of Sciences of the United States of America logoLink to Proceedings of the National Academy of Sciences of the United States of America
. 1974 Oct;71(10):4106–4110. doi: 10.1073/pnas.71.10.4106

Altered Development of the Rat Brain Serotonergic System after Disruptive Neonatal Experience

Dana Giulian 1, Bruce S McEwen 1, Larissa A Pohorecky 1
PMCID: PMC434337  PMID: 4530288

Abstract

A single disruptive experience, a cold treatment, on postnatal day 1 elevated open-field activity and reduced reaction to handling in rats tested more than 240 days later. Neurochemical mechanisms underlying these behavioral phenomena were examined by monitoring the development of the rat brain serotonergic system. After cold treatment, elevations in 5-hydroxytryptamine levels of a preparation of forebrain plus midbrain could be first detected on postnatal day 16 in both sexes. A more detailed regional dissection of the brain showed that such increases occurred in the cerebrum, midbrain, septum-thalamus, and hypothalamus-preoptic area. Rats treated on postnatal days 1 or 6 showed increased 5-hydroxytryptamine levels, whereas animals treated on postnatal day 10 did not, a finding that points to a possible “critical period” of sensitivity. Results of adrenalectomy and corticosterone injections suggest that the influence of the adrenal gland cannot account for the elevation in brain serotonin. Furthermore, the gonadal steroids, estradiol and testosterone, alter brain 5-hydroxytryptamine independently of early experience, as distinguished by the time of appearance, periods of sensitivity, and the direction of monoamine changes. These findings are discussed in relation to the maturation of the neuroendocrine systems governing adrenal and gonadal function.

Keywords: brain 5-hydroxytryptamine, gonadal axis, adrenal axis

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Selected References

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  1. Allen C., Kendall J. W. Maturation of the circadian rhythm of plasma corticosterone in the rat. Endocrinology. 1967 May;80(5):926–930. doi: 10.1210/endo-80-5-926. [DOI] [PubMed] [Google Scholar]
  2. Archer J. Tests for emotionality in rats and mice: a review. Anim Behav. 1973 May;21(2):205–235. doi: 10.1016/s0003-3472(73)80065-x. [DOI] [PubMed] [Google Scholar]
  3. BOVARD E. W. The effects of early handling on viability of the albino rat. Psychol Rev. 1958 Sep;65(5):257–271. doi: 10.1037/h0046608. [DOI] [PubMed] [Google Scholar]
  4. Bartová A. Functioning of the hypothalamo-pituitary-adrenal system during postnatal development in rats. Gen Comp Endocrinol. 1968 Apr;10(2):235–239. doi: 10.1016/0016-6480(68)90030-0. [DOI] [PubMed] [Google Scholar]
  5. Blizard D. A. Individual differences in autonomic responsivity in the adult rat. Neonatal influences. Psychosom Med. 1971 Sep-Oct;33(5):445–457. doi: 10.1097/00006842-197109000-00006. [DOI] [PubMed] [Google Scholar]
  6. Burghardt G. M., Hess E. H. Food imprinting in the snapping turtle, Chelydra serpentina. Science. 1966 Jan 7;151(3706):108–109. doi: 10.1126/science.151.3706.108. [DOI] [PubMed] [Google Scholar]
  7. DENENBERG V. H., CARLSON P. V., STEPHENS M. W. Effects of infantile shock upon emotionality at weaning. J Comp Physiol Psychol. 1962 Oct;55:819–820. doi: 10.1037/h0045414. [DOI] [PubMed] [Google Scholar]
  8. GOTTLIEB G. IMPRINTING IN RELATION TO PARENTAL AND SPECIES IDENTIFICATION BY AVIAN NEONATES. J Comp Physiol Psychol. 1965 Jun;59:345–356. doi: 10.1037/h0022045. [DOI] [PubMed] [Google Scholar]
  9. Giulian D., Pohorecky L. A., McEwen B. S. Effects of gonadal steroids upon brain 5-hydroxytryptamine levels in the neonatal rat. Endocrinology. 1973 Dec;93(6):1329–1335. doi: 10.1210/endo-93-6-1329. [DOI] [PubMed] [Google Scholar]
  10. Howard E., Granoff D. M. Increased voluntary running and decreased motor coordination in mice after neonatal corticosterone implantation. Exp Neurol. 1968 Dec;22(4):661–673. doi: 10.1016/0014-4886(68)90155-6. [DOI] [PubMed] [Google Scholar]
  11. Ladosky W., Gaziri L. C. Brain serotonin and sexual differentiation of the nervous system. Neuroendocrinology. 1970;6(3):168–174. doi: 10.1159/000121920. [DOI] [PubMed] [Google Scholar]
  12. Levine S., Mullins R. F., Jr Hormonal influences on brain organization in infant rats. Science. 1966 Jun 17;152(3729):1585–1592. doi: 10.1126/science.152.3729.1585. [DOI] [PubMed] [Google Scholar]
  13. Mabry P. D., Campbell B. A. Ontogeny of serotonergic inhibition of behavioral arousal in the rat. J Comp Physiol Psychol. 1974 Feb;86(2):193–201. doi: 10.1037/h0035946. [DOI] [PubMed] [Google Scholar]
  14. Murphy B. E. Some studies of the protein-binding of steroids and their application to the routine micro and ultramicro measurement of various steroids in body fluids by competitive protein-binding radioassay. J Clin Endocrinol Metab. 1967 Jul;27(7):973–990. doi: 10.1210/jcem-27-7-973. [DOI] [PubMed] [Google Scholar]
  15. Quattropani S. L., Weisz J. Conversion of progesterone to estrone and estradiol in vitro by the ovary of the infantile rat in relation to the development of its interstitial tissue. Endocrinology. 1973 Dec;93(6):1269–1276. doi: 10.1210/endo-93-6-1269. [DOI] [PubMed] [Google Scholar]
  16. SCHAEFER T., Jr Early "experience" and its effects on later behavioral processes in rats. II. A critical factor in the early handling phenomenon. Trans N Y Acad Sci. 1963 Jun;25:871–889. doi: 10.1111/j.2164-0947.1963.tb01925.x. [DOI] [PubMed] [Google Scholar]
  17. Schapiro S. Some physiological, biochemical, and behavioral consequences of neonatal hormone administration: cortisol and thyroxine. Gen Comp Endocrinol. 1968 Apr;10(2):214–228. doi: 10.1016/0016-6480(68)90028-2. [DOI] [PubMed] [Google Scholar]
  18. Zarrow M. X., Campbell P. S., Denenberg V. H. Handling in infancy: increased levels of the hypothalamic corticotropin releasing factor (CRF) following exposure to a novel situation. Proc Soc Exp Biol Med. 1972 Oct;141(1):356–358. doi: 10.3181/00379727-141-36776. [DOI] [PubMed] [Google Scholar]

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