A-582941, cholinergic alpha 7 nicotinic receptor agonist, improved cognitive and negative symptoms of the sub-chronic MK-801 model of schizophrenia in rats

Gokhan Unal,Feyza Aricioglu

doi:10.1080/24750573.2017.1379716

Abstract

ABSTRACTOBJECTIVESNicotinic receptor systems are involved in a wide variety of behavioural functions, including cognitive function, and nicotinic medications, may provide beneficial treatment for cognitive dysfunctions such as schizophrenia. According to the results of postmortem studies of schizophrenic patients, alpha 7 nicotinic acethylcholine receptor (α7 NAChR) binding levels and protein expressions were found to be decreased in cognition-related areas such as hippocampus and prefrontal cortex. In addition to this the fact that the prevalence of tobacco consumption is greater than healthy individuals encouraged research of nicotinic receptors in schizophrenia pathogenesis and treatment. In this study, we examined the effect of A-582941, a partial agonist of α7 NAChR, in the sub-chronic MK-801 model of schizophrenia in rats.METHODSWistar Hannover rats were divided into five groups as follows and and all drug administrations were done intraperitoneally (i.p.) excluding the last dose of MK-801, which wa...

Highlights

Schizophrenia is a complex and devastating psychiatric disease whose prevalence is estimated to be at least 0.45% by certain studies [1]
It has been shown that Clozapine only improved the defect of following behaviour that represents tendency to socialization, while A-582941 improved both of the impairments on following and avoiding behaviour that were thought to represent social withdrawal of schizophrenia patient
It has been well demonstrated that information processing and sensorimotor gating which are thought to play a role in attention, cognitive function, and daily living are impaired in schizophrenia

Summary

Introduction

Schizophrenia is a complex and devastating psychiatric disease whose prevalence is estimated to be at least 0.45% by certain studies [1]. Positive and negative symptoms such as hallucination, delusion, paranoia, social withdrawal, and anhedonia are more prominent symptoms of schizophrenia, while 80% of schizophrenic patients have cognitive impairments in different types of memory [2]. Even though positive symptoms can be improved by both typical and atypical antipsychotics, negative symptoms and cognitive deficits are still unmet needs for schizophrenia treatment. It has been shown that NMDA receptor antagonists such as phencyclidine (PCP) and ketamine induce psychosis-like behaviours in healthy people [6].

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