The effects of sulpirid on spatial learning in healthy and MAM E-17 schizophrenia model rats
01/30/2020
Daniella Anna Dusa1, 2,Veronika Kállai1, 2, Tamás Ollmann1, 2, Kristóf László1, 2, Erika Kertes1, 2, Beáta Marosné Bartos1, 2, Rita Gálosi1, 2, Olga Zagoracz1, 2, László Lénárd1, 2, 3, László Zoltán Péczely1
1 Institute of Physiology, Pécs University, Medical School
2 Centre for Neuroscience, Pécs University,
3 Molecular Neuroendocrinology and Neurophysiology Research Group, Pécs University, Szentágothai Center
Schizophrenia is a severe psychiatric disease, affecting 1% of the world’s population. Its symptoms include the lack of motivation, reduced emotional expression, false belief, delusions and cognitive disorders.The widely accepted MAM-E17 schizophrenia rat model is based on the neurodevelopmental theory of the disease. In rats, the 17th embryonal day (E17) is critical in the development of the cortico-limbic circuits. Methylazoxymethanol-acetate (MAM) treatment on E17 leads to schizophrenia-like symptoms. The aim of the present experiments was to investigate the cognitive skills and spatial learning of healthy and MAM-E17 rats in the Morris Water Maze (MWM) test microinjecting different doses of D2 dopamine (DA) receptor antagonist sulpiride into the ventral pallidum (VP). Before the behavioral tests, by means of stereotaxic surgery guide cannulae were implanted 0.5 mm above the VP. The D2 DA receptor antagonist was administered through the microinjection cannulae inserted into the guide cannulae. Eight animal groups were created: 4 healthy and 4 MAM E-17 model rat groups (in both cases control animals and animals treated with 0,1 μg, 1 μg and 4 μg sulpiride were used). In the Morris Water Maze (MWM) test the animals had to find the hidden platform in the water. On the 3rd day of the MWM test each healthy animal group found the platform significantly faster than on the first day, however the results of the test swimming (without the platform) show that the sulpiride-treated groups used not spatial but another learning strategy. In the MAM E-17 rat model groups the control group and the 0.1 μg sulpiride-treated group showed significanty better learning abilities compared to the other two MAM E-17 groups. According to our present results learning processes in MAM E-17 rats are particularly sensitive to the intra-VP sulpiride microinjections. This means that the D2 DA antagonist antipsychotic treatment can possibly lead to impaired learning abilities affecting the VP in human patients as well.