1MeTIQ and olanzapine, despite their neurochemical impact, did not ameliorate performance in fear conditioning and social interaction tests in an MK-801 rat model of schizophrenia

Abstract

Background 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. The results obtained after administration of 1MeTIQ were compared with those obtained with olanzapine, an antipsychotic drug. Methods Sprague–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. Results Our 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. Conclusion 1MeTIQ, 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.

Differential Effects of Aripiprazole on Electroencephalography-Recorded Gamma-Band Auditory Steady-State Response, Spontaneous Gamma Oscillations and Behavior in a Schizophrenia Rat Model

“…One rat study, for instance, found that aripiprazole administered at lower doses than those used in our study could reverse the social interaction deficit induced by an acute administration of MK-801 [59]. On the other hand, other studies found that aripiprazole used at comparable doses as well as other atypical antipsychotics such as olanzapine, risperidone and clozapine had no effect on the social deficit provoked by MK-801 or PCP [32,[60][61][62], which perfectly aligns with our results. Hence, it is possible that the lack of effect of aripiprazole was either because the dose tested was too strong or because it was not able to produce an effect on the root cause of social dysfunction.…”

Modulation of the endoplasmic reticulum stress and unfolded protein response mitigates the behavioral effects of early-life stress

“…Behavioral tests were performed and analyzed using a computer-controlled FC system (TSE, Bad Homburg, Germany) as described previously by Chocyk et al [ 38 ] and Bialon et al [ 51 ]. Each FC unit consisted of sound-attenuating housing with a loudspeaker, camera, ventilation fan and 4 symmetrically mounted lamps in the ceiling construction and test box.…”

Advantages and Limitations of Animal Schizophrenia Models

“…MK-801 is commonly used in mice and rats [ 98 , 99 ]; however, it is less often found in zebrafish [ 100 ] and monkey [ 101 ] studies. In rodents, the behavioral effects of MK-801 include working perturbations [ 102 , 103 ], hyperlocomotion [ 103 , 104 ], deficits in PPI [ 102 , 104 ], lowered sociability [ 103 , 105 , 106 ], and fear conditioning perturbations [ 106 , 107 ]. Notably, the data presenting MK-801-induced anxiety behavior seem to be rather inconsistent; some studies show the anxiogenic effects of MK-801 administration [ 105 ], while other studies present undisturbed anxiety-related behavior [ 104 , 108 ].…”