S207. CHRONIC TREATMENT WITH 1METIQ INDUCES PRO-COGNITIVE EFFECT ON RECOGNITION MEMORY IN KETAMINE MODEL OF SCHIZOPHRENIA IN RATS

Abstract

BackgroundSchizophrenia is severe mental disorder that affects 1% of world population and cause long-term disability (Mueser and McGurk, 2004). Manifestation of the illness can be distinguished into three groups – positive, negative and cognitive symptoms (van Os, 2009). However, cognitive ones (e.g. memory deficits) seem to remain resistant to pharmacotherapy (Cerveri et al., 2019). Memory deficits, as a symptoms of schizophrenia, may be modeled in animals by using a specified dose of ketamine and measured in novel object recognition (NOR) test (Lafionatis et al., 2019). 1-methyl-1,2,3,4-tetrahydroisoquinoline (1MeTIQ) is an endogenous amine present and synthesized in the mammalian brain with neuroprotective properties (Antkiewicz-Michaluk et al., 2014) and our last study have shown anxiolytic action of 1MeTIQ in rat model of schizophrenia (Wąsik et al., 2019) therefore we decided to define a potential of 1MeTIQ to exhibit pro-cognitive effect on memory in ketamine-treated rats.MethodsNOR test consisted of adaptation (24h before testing) and two phases (T1 and T2, with 1-hour interval). Exploration times of each objects, preference (PI) and discrimination (DI) indexes were measured. Microdialysis was performed to asses glutamate release in frontal cortex. Male Sprague Dawley rats were divided into 4 groups. The control group received saline injections. Animals received acute ketamine (20mg/kg, i.p.) or chronic (7x) administration of1MeTIQ (50mg/kg, i.p.). The combined group received single dose of ketamine 30 minutes after last dose of 1MeTIQ.ResultsIn T1 phase of NOR, there were no changes between exploration times of two identical objects. In T2 phase with two different objects, we observed no significant changes in group treated with ketamine. 1MeTIQ given alone increased the difference between time of objects exploration. In combined group, 1MeTIQ completely reversed the effect of ketamine. Ketamine tended, however, without statistical significance, to decrease PI and DI. Treatment with 1MeTIQ did not change mentioned indexes. In microdialysis study, we observed no significant changes in glutamate release in any group.DiscussionWe demonstrated that chronic administration of 1MeTIQ may improve recognition memory function. However, we didn’t observe changes in glutamate release. We suggest that pro-cognitive effect of 1MeTIQ is associated with its impact on monoamine metabolism.