title: Spatial memory is impaired by peripubertal GnRH agonist treatment and testosterone replacement in sheep.
abstract: Chronic gonadotropin-releasing hormone agonist (GnRHa) is used therapeutically to block activity within the reproductive axis through down-regulation of GnRH receptors within the pituitary gland. GnRH receptors are also expressed in non-reproductive tissues, including areas of the brain such as the hippocampus and amygdala. The impact of long-term GnRHa-treatment on hippocampus-dependent cognitive functions, such as spatial orientation, learning and memory, is not well studied, particularly when treatment encompasses a critical window of development such as puberty. The current study used an ovine model to assess spatial maze performance and memory of rams that were untreated (Controls), had both GnRH and testosterone signaling blocked (GnRHa-treated), or specifically had GnRH signaling blocked (GnRHa-treated with testosterone replacement) during the peripubertal period (8, 27 and 41 weeks of age). The results demonstrate that emotional reactivity during spatial tasks was compromised by the blockade of gonadal steroid signaling, as seen by the restorative effects of testosterone replacement, while traverse times remained unchanged during assessment of spatial orientation and learning. The blockade of GnRH signaling alone was associated with impaired retention of long-term spatial memory and this effect was not restored with the replacement of testosterone signaling. These results indicate that GnRH signaling is involved in the retention and recollection of spatial information, potentially via alterations to spatial reference memory, and that therapeutic medical treatments using chronic GnRHa may have effects on this aspect of cognitive function.
authors.affiliation: Institute of Biodiversity Animal Health and Comparative Medicine, College of Medical Veterinary and Life Sciences, University of Glasgow, Glasgow, G61 1QH, UK.
authors.forename: D
authors.initials: D
authors.lastname: Hough
authors.affiliation: Institute of Biodiversity Animal Health and Comparative Medicine, College of Medical Veterinary and Life Sciences, University of Glasgow, Glasgow, G61 1QH, UK.
authors.forename: M
authors.initials: M
authors.lastname: Bellingham
authors.affiliation: Department of Medical Neurobiology, Division of Clinical Neuroscience, Oslo University Hospital - Rikshospitalet, 0027, Oslo, Norway.
authors.forename: I R H
authors.initials: IRH
authors.lastname: Haraldsen
authors.affiliation: Division of Veterinary Bioscience and Education, School of Veterinary Medicine, College of Medical Veterinary and Life Sciences, University of Glasgow, Glasgow, G61 1QH, UK.
authors.forename: M
authors.initials: M
authors.lastname: McLaughlin
authors.affiliation: Institute of Biodiversity Animal Health and Comparative Medicine, College of Medical Veterinary and Life Sciences, University of Glasgow, Glasgow, G61 1QH, UK.
authors.forename: M
authors.initials: M
authors.lastname: Rennie
authors.affiliation: Institute of Biodiversity Animal Health and Comparative Medicine, College of Medical Veterinary and Life Sciences, University of Glasgow, Glasgow, G61 1QH, UK.
authors.forename: J E
authors.initials: JE
authors.lastname: Robinson
authors.affiliation: Department of Medical Neurobiology, Division of Clinical Neuroscience, Oslo University Hospital - Rikshospitalet, 0027, Oslo, Norway; Department of Psychology, University of Oslo, Pb 1094 Blindern, 0317 Oslo, Norway; Department of Neuropsychology, Helgeland Hospital, Mosjøen, Norway.
authors.forename: A K
authors.initials: AK
authors.lastname: Solbakk
authors.affiliation: Institute of Biodiversity Animal Health and Comparative Medicine, College of Medical Veterinary and Life Sciences, University of Glasgow, Glasgow, G61 1QH, UK. Electronic address: Neil.Evans@glasgow.ac.uk.
authors.forename: N P
authors.initials: NP
authors.lastname: Evans
mesh_terms: D000367:Age Factors; D000818:Animals; D007987:Gonadotropin-Releasing Hormone / Q000819:agonists* / Q000494:pharmacology*; D008297:Male; D000072458:Orientation, Spatial / Q000187:drug effects*; D012756:Sheep; D015398:Signal Transduction / Q000502:physiology*; D065853:Spatial Learning / Q000187:drug effects*; D065852:Spatial Memory / Q000187:drug effects*; D013739:Testosterone / Q000494:pharmacology*
chemical_list: D007987:Gonadotropin-Releasing Hormone; D013739:Testosterone
keywords: Gender dysphoria; GnRH; Hippocampus; Puberty; Spatial memory; Spatial orientation