Gonadotrophin-releasing hormone agonists (GnRHa) are commonly used to suppress the reproductive axis. In adults this is typically over short time periods (i.e. 3 months) as a co-treatment for hormone sensitive tumours, fibroids and in vitro fertilization techniques. GnRHa, however, are chronically prescribed to children to delay the onset of puberty in conditions such as precocious puberty and gender identity disorder. GnRH-receptors have been documented throughout the body, including brain regions such as the hippocampus, hypothalamus and amygdala. Effects of prolonged treatment with GnRHa may thus be more extensive than direct reproductive effects. This BBSRC-funded study investigated the effect of GnRHa treatment, to delay the onset of puberty, on long term spatial orientation and long term memory (hippocampus-dependent functions) in sheep. Three groups of rams were compared to tease apart the effects of GnRH and sex steroids, namely a control group (n=23); a group receiving GnRHa treatment (n=23); and a group receiving both GnRHa treatment and testosterone replacement therapy (n=22). Results showed that the rams’ ability to complete a maze increased with age (assessed 8, 28 and 42 weeks of age) but was not influenced by GnRHa treatment (Two-way ANOVA: Interaction P=0.7313; Treatment P=0.9664; Age P<0.0001). After training at 43 weeks (criteria: completion<1min), spatial memory was assessed one month later and showed that control rams tended to complete the maze quicker (1.15±0.28min, n=19) compared to GnRHa rams (1.45±0.25min, n=19), while testosterone treatment attenuated this trend (1.97±0.37min, n=22) (Kruskal-Wallis: P=0.0683). Presentation of rams with a modified maze layout showed individual variation and no significant difference between the groups to complete the maze (One-way ANOVA: P=0.4628). It seems likely that the ability to solve spatial problems is a function of developmental changes rather than GnRHa treatment, whereas the retention of spatial memory might be affected by GnRHa treatment.