GHB, a popularly known drug as "liquid ecstasy", is a substance with abuse potential. Among the possible described side-effects after the continued consumption of GHB are amnesia and deterioration of memory. Likewise, recent studies indicate the existence of neurotoxicity in certain brain regions after its prolonged treatment. The aim of this study was to examine the effect of the subchronic administration of GHB (10 and 100 mg/kg) on spatial memory and sensoriomotor reflexes in male rats, using the Morris water maze and a battery of sensoriomotor tests, respectively. The results indicated that animals treated with GHB (10 mg/kg) showed a greater latency of escape during the phase of acquisition in the days first and third of tests, as compared with the control group (p<0.05), as well as a deterioration of grasping reflex with the two doses of GHB (p<0.01). Numerous studies indicated that the medial prefrontal cortex is a crucial neuronal substrate in the working memory and grasping reflex modulation. These results suggest that prolonged administration of GHB could alter structure and/or function of the medial prefrontal cortex, as well as its interconnections with other brain regions involved in the evaluated cognitive and neurological processes.