Comparison of the effects of 1MeTIQ and olanzapine on performance in the elevated plus maze test and monoamine metabolism in the brain after ketamine treatment

Abstract

Anxiety is a common symptom of schizophrenia. Ketamine, which acts as a noncompetitive antagonist of glutamatergic NMDA receptors by binding to the phencyclidine site, may induce schizophrenia-like symptoms and promote anxiogenic-like behaviour. The symptoms of anxiety in rodents can be measured by the elevated plus maze (EPM) test. 1-Methyl-1,2,3,4-tetrahydroisoquinoline (1MeTIQ), as a neuroprotective and antiaddictive substance, produces pharmacological effects by influencing monoaminergic and glutamatergic activity, as previously demonstrated by us. The aim of the present study was to investigate the anxiolytic-like potential of 1MeTIQ after the administration of ketamine. These results were compared to the effects of olanzapine, an antipsychotic drug commonly used in the treatment of schizophrenia. We conducted the EPM test, during which the percentage of time spent in and the number of entries into the open arms were measured. In addition, locomotor activity was measured. Furthermore, we conducted biochemical analyses to verify changes in the levels of neurotransmitters and their metabolites in selected rat brain structures. Behavioural analyses showed that 1MeTIQ, similar to olanzapine, completely inhibited ketamine-induced anxiogenic effects in the EPM test. On the other hand, neurochemical data indicated that 1MeTIQ, as a reversible inhibitor of MAO, significantly blocked the dopamine MAO-dependent oxidation pathway, whereas olanzapine significantly increased the activity of this pathway. The results above suggest that the anxiolytic-like properties of 1MeTIQ are connected to its influence on the catabolism of dopamine, the elevation of serotonin concentrations and the reduction in the levels of noradrenaline.