Peripubertal GnRH and testosterone co-treatment leads to increased familiarity preferences in male sheep

Hough, D. , Robinson, J.E. , Bellingham, M. , Fleming, L.M., McLaughlin, M. , Jama, K., Haraldsen, I.R.H., Solbakk, A.K. and Evans, N.P. (2019) Peripubertal GnRH and testosterone co-treatment leads to increased familiarity preferences in male sheep. Psychoneuroendocrinology, 108, pp. 70-77. (doi: 10.1016/j.psyneuen.2019.06.008) (PMID:31229635) (PMCID:PMC6712355)

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Chronic gonadotropin-releasing hormone agonist (GnRHa) treatment is effective for the medical suppression of the hypothalamic-pituitary-gonadal axis in situations like central precocious puberty and gender dysphoria. However, its administration during the peripubertal period could influence normal brain development and function because GnRH receptors are expressed in brain regions that regulate emotions, cognition, motivation and memory. This study used an ovine model to determine whether chronic peripubertal GnRHa-treatment affected the developmental shift from preference of familiarity to novelty. Experimental groups included Controls and GnRHa-treated rams. To differentiate between effects of altered GnRH signaling and those associated with the loss of sex steroids, a group was also included that received testosterone replacement as well as GnRHa (GnRHa + T). Preference for a novel versus familiar object was assessed during 5-min social isolation at 8, 28 and 46 weeks of age. Approach behavior was measured as interactions with and time spent near the objects, whereas avoidance behavior was measured by time spent in the entrance zone and attempts to escape the arena via the entry point. Emotional reactivity was measured by the number of vocalizations, escape attempts and urinations. As Control and GnRHa-treated rams aged, their approach behaviors showed a shift from preference for familiarity (8 weeks) to novelty (46 weeks). In contrast, relative to the Controls the GnRHa + T rams exhibited more approach behaviors towards both objects, at 28 and 46 weeks of age and preferred familiarity at 46 weeks of age. Vocalisation rate was increased in GnRHa treated rams in late puberty (28 weeks) compared to both Control and GnRHa + T rams but this effect was not seen in young adulthood (46 weeks). These results suggest that the specific suppression of testosterone during a developmental window in late puberty may reduce emotional reactivity and hamper learning a flexible adjustment to environmental change. The results also suggest that disruption of either endogenous testosterone signalling or a synergistic action between GnRH and testosterone signalling, may delay maturation of cognitive processes (e.g. information processing) that affects the motivation of rams to approach and avoid objects.

Item Type:Articles
Glasgow Author(s) Enlighten ID:McLaughlin, Dr Mark and Robinson, Dr Jane and Bellingham, Dr Michelle and Evans, Professor Neil and Hough, Dr Denise and Fleming, Mrs Lynne
Authors: Hough, D., Robinson, J.E., Bellingham, M., Fleming, L.M., McLaughlin, M., Jama, K., Haraldsen, I.R.H., Solbakk, A.K., and Evans, N.P.
College/School:College of Medical Veterinary and Life Sciences
College of Medical Veterinary and Life Sciences > School of Biodiversity, One Health & Veterinary Medicine
Journal Name:Psychoneuroendocrinology
ISSN (Online):1873-3360
Published Online:13 June 2019
Copyright Holders:Copyright © 2019 The Authors
First Published:First published in Psychoneuroendocrinology 108:70-77
Publisher Policy:Reproduced under a Creative Commons License

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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
536311Effects of GnRH blockade on neurocognitive and physiological endpoints.Neil EvansBiotechnology and Biological Sciences Research Council (BBSRC)BB/K002821/1RI BIODIVERSITY ANIMAL HEALTH & COMPMED