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

PSYCHONEUROENDOCRINOLOGY

卷:108

Article

Hough, D.¹  Robinson, J. E.¹  Bellingham, M.¹  Fleming, L. M.¹  McLaughlin, M.³  Jama, K.¹  Haraldsen, I. R. H.²  Solbakk, A. K.^4,5,6  Evans, N. P.¹ 

[1] Univ Glasgow, Inst Biodivers Anim Hlth & Comparat Med, Coll Med Vet & Life Sci, Glasgow G61 1QH, Lanark, Scotland

[2] Oslo Univ Hosp, Rikshosp, Dept Neuropsychiat & Psychosomat Med, Div Surg & Clin Neurosci, N-0027 Oslo, Norway

[3] Univ Glasgow, Sch Vet Med, Coll Med Vet & Life Sci, Glasgow G61 1QH, Lanark, Scotland

[4] Oslo Univ Hosp, Rikshosp, Div Surg & Clin Neurosci, Dept Neurosurg, N-0027 Oslo, Norway

[5] Univ Oslo, Dept Psychol, Pb 1094 Blindern, N-0317 Oslo, Norway

[6] Helgeland Hosp, Dept Neuropsychol, N-8607 Mosjoen, Norway

关键词: Novelty;    GnRH;    Testosterone;    Cognition;    Motivation;    Puberty;   

DOI  :  10.1016/j.psyneuen.2019.06.008

来源: Elsevier

【 摘 要 】

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.

【 授权许可】

Free