Enhanced novelty-induced corticosterone spike and upregulated serotonin 5-HT1A and cannabinoid CB1 receptors in adolescent BTBR mice

Georgianna G. Gould, Teresa F. Burke, Miguel D. Osorio, Corey M. Smolik, Wynne Q. Zhang, Emmanuel S. Onaivi, Ting Ting Gu, Mauris N. DeSilva, Julie G. Hensler

Research output: Contribution to journalArticle

13 Scopus citations

Abstract

Hypothalamic pituitary adrenal (HPA) axis responses to change and social challenges during adolescence can influence mental health and behavior into adulthood. To examine how HPA tone in adolescence may contribute to psychopathology, we challenged male adolescent (5 weeks) and adult (16 weeks) BTBR T+tf/J (BTBR) and 129S1/SvImJ (129S) mice with novelty in sociability tests. In prior studies these strains had exaggerated or altered HPA stress responses and low sociability relative to C57BL/6J mice in adulthood. In adolescence these strains already exhibited similar or worse sociability deficits than adults or age-matched C57 mice. Yet BTBR adolescents were less hyperactive and buried fewer marbles than adults. Novelty-induced corticosterone (CORT) spikes in adolescent BTBR were double adult levels, and higher than 129S or C57 mice at either age. Due to their established role in HPA feedback, we hypothesized that hippocampal Gαi/o-coupled serotonin 5-HT1A and cannabioid CB1 receptor function might be upregulated in BTBR mice. Adolescent BTBR mice had higher hippocampal 5-HT1A density as measured by [3H] 8-hydroxy-2-(di-n-propylamino) tetralin (8-OH-DPAT) binding than C57 mice, and adult BTBR 8-OH-DPAT-stimulated GTPγS binding was higher than in either C57 or 129S mice in this region. Further, BTBR hippocampal CB1 density measured by [3H]CP55,940 binding was 15-20% higher than in C57. CP55,940-stimulated GTPγS binding in adult BTBR dentate gyrus was 30% higher then 129S (p<0.05), but was not a product of greater neuronal or cell density defined by NeuN and DAPI staining. Hence hyperactive HPA responsiveness during adolescence may underlie 5-HT1A and CB1 receptor up-regulation and behavioral phenotype of BTBR mice.

Original languageEnglish (US)
Pages (from-to)158-169
Number of pages12
JournalPsychoneuroendocrinology
Volume39
Issue number1
DOIs
StatePublished - Jan 1 2014

Keywords

  • 129S1/SvImJ
  • Adolescent
  • BTBR
  • C57BL
  • Cannabinoid
  • GTPγS autoradiography
  • HPA feedback
  • Hippocampus
  • Serotonin
  • Social behavior

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Endocrinology
  • Endocrine and Autonomic Systems
  • Psychiatry and Mental health
  • Biological Psychiatry

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    Gould, G. G., Burke, T. F., Osorio, M. D., Smolik, C. M., Zhang, W. Q., Onaivi, E. S., Gu, T. T., DeSilva, M. N., & Hensler, J. G. (2014). Enhanced novelty-induced corticosterone spike and upregulated serotonin 5-HT1A and cannabinoid CB1 receptors in adolescent BTBR mice. Psychoneuroendocrinology, 39(1), 158-169. https://doi.org/10.1016/j.psyneuen.2013.09.003