Effects of acethylcholinesterase inhibitors on baseline and scopolamine-induced distripution of prepulse inhibition (PPI)

Previous studies have shown that the cholinergic system has an important role in positive and cognitive disorders associated with schizophrenia. This study aimed to investigate the effects of acethylcholinesterase inhibitors (AChEI) galantamine and physostigmine on sensorimotor gating dysfunction, which reflects the positive and cognitive pathology observed in schizophrenia. Effects of galantamine and physostigmine in the study were investigated with both Low-High schizophrenia model based on individual differences and experimental pharmacological schizophrenia model. In our study, the PPI test was used to measure sensorimotor gating function. In the first model, changes in PPI values were observed by treating galantamine (1 mg / kg; i.p) and physostigmine (0,4 mg / kg; i.p.) to the experimental animals which were separated to have low and high inhibition levels according to the PPI values. No significant change in PPI was obtained with physostigmine while galantamine increased the PPI in the low group compared to baseline values. In the high group, no significant effect was observed with either drug. In the second step, in which the pharmacological model was performed using scopolamine (0,4 mg / kg; i.p.) galantamine and physostigmine reversed the decrease in PPI values induced by scopolamine. In conclusion, our findings show that the AChEIs; galantamine and physostigmine reversed the pharmacologically-induced disruption, while the disruption in experimental animals caused by natural seperation could only be reversed by galantamine. That pathology of low inhibition in animals determined by natural seperation is more complex than that in the scopolamine-induced model; galantamine has a broader spectrum effect than physostigmine. Our results suggest that acetylcholinesterase inhibitors may exhibit beneficial effects in the treatment of diseases in which PPI disruption is observed, particularly schizophrenia. Key words: Schizophrenia, Prepulse Inhibition (PPI) ,galantamine, physostigmine, cognitive impairments