FAP modulators(University of Antwerp)

GPR35 is an orphan receptor expressed in astrocytes and neurons of the central nervous system (CNS), including the hippocampus; however, its role in cognitive functions is largely unknown. This study administered intra-hippocampal injections of compound-10 (a GPR35-selective agonist), ML194 (a GPR35-selective antagonist), and the combination of both to elucidate their pharmacological actions in the Barnes maze. Compared to the vehicle (10 % DMSO) and ML194 groups, animals treated with the compound-10 showed a higher latency and longer distance to solve the maze (p < 0.05) (an effect prevented by pretreatment with ML194). Compound-10 increased immobility, suggesting an anxiogenic effect, and decreased average speed compared to the vehicle and ML194 groups (p < 0.05); both actions were prevented by pretreatment with ML194. In the spatial memory test, both the vehicle and ML194 groups showed a preference for the target quadrant (i.e., the quadrant with the tunnel escape) compared with non-target quadrants (p < 0.05). No preference was detected among quadrats in the compound-10 group. ML194 prevented the above memory impairment. Regarding the navigation strategies, no differences were detected among treatments in the serial strategy. Animals from the compound-10 group showed an increased use of random-strategy compared to the vehicle and ML194 groups (p < 0.05). Animals from the ML194 group exhibited an increased use of spatial strategy compared to the compound-10 and combination groups (p < 0.05). Our results suggest that pharmacological stimulation of hippocampal GPR35 interferes with spatial learning, memory, and navigation, and seems to modulate anxiety.