Abstract
BackgroundThe aim of the present study was to evaluate the effect of 1MeTIQ on fear memory and social interaction in an MK-801-induced model of schizophrenia. The results obtained after administration of 1MeTIQ were compared with those obtained with olanzapine, an antipsychotic drug.MethodsSprague–Dawley rats received a single injection of MK-801 to induce behavioral disorders. 1MeTIQ was given either acutely in a single dose or chronically for 7 consecutive days. Olanzapine was administered once. In groups receiving combined treatments, 1MeTIQ or olanzapine was administered 20 min before MK-801 injection. Contextual fear conditioning was used to assess disturbances in fear memory (FM), and the sociability of the rats was measured in the social interaction test (SIT). Biochemical analysis was carried out to evaluate monoamine levels in selected brain structures after treatment.ResultsOur results are focused mainly on data obtained from neurochemical studies, demonstrating that 1MeTIQ inhibited the MK-801-induced reduction in dopamine levels in the frontal cortex and increased the 5-HT concentration. The behavioral tests revealed that acute administration of MK-801 caused disturbances in both the FM and SIT tests, while neither 1MeTIQ nor olanzapine reversed these deficits.Conclusion1MeTIQ, although pharmacologically effective (i.e., it reverses MK-801-induced changes in monoamine activity), did not influence MK-801-induced social and cognitive deficits. Thus, our FM tests and SIT did not support the main pharmacological hypotheses that focus on dopamine system stabilization and dopamine–serotonin system interactions as probable mechanisms for inhibiting the negative symptoms of schizophrenia.
Highlights
Schizophrenia is a devastating mental illness that occurs in 1% of the population worldwide and may be characterized by emotional impairment, cognitive deficits, and social dysfunction [1]
Post hoc tests showed a significantly decreased DA level in animals treated with MK-801 compared to saline (p < 0.001), and this effect was reversed by an acute dose of either 1MeTIQ or olanzapine
An acute dose of 1MeTIQ decreased locomotor activity in rats and completely inhibited the locomotor hyperactivity induced by MK-801 [33]. 1MeTIQ antagonized some neurochemical and behavioral effects of MK-801, but it did not reverse the behavioral disorders caused by MK-801 in the fear memory (FM) and social interaction test (SIT) tests
Summary
Schizophrenia is a devastating mental illness that occurs in 1% of the population worldwide and may be characterized by emotional impairment, cognitive deficits, and social dysfunction [1]. Thereby, animals develop a fear of both the tone and the training context, and the memory of that fear is measured by assessing freezing time, which is a natural, adaptive and speciesspecific reaction to threat [4, 5]. The aim of the present study was to evaluate the effect of 1MeTIQ on fear memory and social interaction in an MK-801-induced model of schizophrenia. Contextual fear conditioning was used to assess disturbances in fear memory (FM), and the sociability of the rats was measured in the social interaction test (SIT). The behavioral tests revealed that acute administration of MK-801 caused disturbances in both the FM and SIT tests, while neither 1MeTIQ nor olanzapine reversed these deficits. Conclusion 1MeTIQ, pharmacologically effective (i.e., it reverses MK-801-induced changes in monoamine activity), did not influence MK-801-induced social and cognitive deficits. Our FM tests and SIT did not support the main pharmacological hypotheses that focus on dopamine system stabilization and dopamine–serotonin system interactions as probable mechanisms for inhibiting the negative symptoms of schizophrenia
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