Effects of γ-hydroxybutyric acid on spatial learning and memory in adolescent and adult female rats

γ-hydroxybutyric acid (GHB) has been reported to disrupt spatial learning and memory in adolescent male rats. The present study was undertaken to determine the effects of GHB on the acquisition of spatial memory in adolescent female rats, and to investigate age specificity of the behavioral impairments. Adolescent female rats were subjected to repeated GHB or saline administrations, and tested in the Morris water maze. Compared to age-matched saline controls, adolescent GHB-treated rats took significantly longer and swam greater distances to find the hidden platform. In the probe trial, GHB-treated adolescent rats spent less time in the target quadrant than saline-treated controls. There was no difference in either the swim speed or in the visual task performance between GHB-treated and saline-treated rats. To test for ontogenic specificity of the behavioral responses, adult female rats were treated with GHB and tested behaviorally in two separate experiments using a 6-day learning protocol (Experiment 1) and a 16-day learning protocol (Experiment 2). In the 6-day spatial learning and memory task, adult saline-treated rats failed to learn the task, and GHB did not alter the latency to find the platform, or performance in the probe trial. In the second behavioral protocol, a modified version of the memory task was used to test adult animals. The number of test days was increased from 6 days to 16 days. Adult saline-treated females learned the task in the 16-days protocol. But unlike adolescent female rat, GHB in adult rats had minimal effects on reference memory even when they had learned the spatial memory task. Performances in the probe trial by adult GHB-treated rats and saline controls were similar. Together, these data suggest that GHB impairs spatial learning specifically in adolescent female rats.