Effects of G-protein-coupled receptor 30 agonist G-1 on spatial memory in adult female rats

Abstract

Ovarian hormones such as estradiol are known to have a complex relationship with spatial cognition. Despite many inconsistencies within the literature, estradiol can enhance spatial memory consolidation on a water maze task when administered during a critical period post-training. While the rapid effects of estradiol on consolidation have been established, the mechanism responsible for them is still unknown. The primary objective of the current study was to determine if activation of the membrane bound G-protein-receptor 30 (GPR30) by estradiol is responsible for the enhanced consolidation. Data were collected from forty adult ovariectomized female rats, divided into three groups that were treated either with the GPR30 specific agonist G-1 immediately following training, G-1 two hours following training, or sesame oil vehicle immediately following training. Rats underwent eight training trials on a water maze task with a fixed hidden escape platform. Twenty-four hours after the completion of training and treatment, all subjects completed four retention trials on the same task. Latency to reach the platform and percent of pathlength spent in the quadrant containing the platform during the first probe trial were used as measures of successful consolidation of spatial learning. There was no significant difference in performance on the probe trials between rats treated with G-1 and sesame oil, indicating that GPR30 activation is not sufficient to enhance consolidation of spatial memory. However, it is important to interpret these results against a backdrop of differences in experimental design between the existing literature and the current study including G-1 dose, type of vehicle, and administration regime, spatial cognition task, and the component of cognition studied. This study offers insight into potential receptor specific therapies for treatment of memory loss in post-menopausal women.