Kisspeptin and its membran receptor (GPR54) are expressed in various brain regions, especially in the hypothalamus, hippocampus and cortex. Effects of this neuropeptide on reproductive functions and puberty onset have been investigated. However, functions of kisspeptin/GPR54 system in the hippocampus have not been clarified. Therefore, we have examined effects of kisspeptin and its antagonist on learning, memory, animal activity, depression and anxiety behavior and their underlying mecanisms. Adult female Sprague Dawley rats were devided three groups (n=8/group): Control animals received saline (osmotic minipump, icv) for 28 days. Rats in the second and third groups were administered with osmotic minipump driven infusion of kisspeptin-10 (10 nmol/kg/day, icv) and kisspeptin antagonist (p234; 10 nmol/kg/day, icv), respectively. Alzet miniosmotic pump and icv infusion kits were inserted by using a stereotaxic frame under anaesthetised with a mixture of ketamine (75mg/kg) and Xylazine (5 mg/kg). The experiments were approved by the local ethics committee. Cognitive functions (using Barnes maze), animal activity, anxiety behavior were determined before and after the treatment period. At the end, all animals were decapitated, brains removed and frozen. Coronal brain sections (15 µ) were cut. Number of neurons, changes in ERK1/2 of phosphorilation, NCAM and PSD-95 protein expression in hippocampus were evaluated by cresyl violet staining and western blotting, respectively. The results were statistically analyzed by using One-Way ANOVA. Kisspeptin significantly increased phosphorilation of ERK 2 (p<0.05). Cresyl violet stained sections showed no difference in the morphology and number of the neurons in the dentate gyrus, CA1, CA2 and CA3 regions of the hippocampus. Treatment with the kisspeptin antagonist significantly increased the distance and duration to find the target box in the Barnes maze (p<0.05) compared to the control group. No significant differences were observed in the other sensory-motor behavioral tests in any of the groups. In conclusion, our findings suggest that chronic inhibition of kisspeptin/GPR54 system in adult animals significantly reduces cognitive functions. Role of exogenous kisspeptin infusion should be studied in a memory deficit animal model.