الفهرس 
PaliperidoneOnly 14 pages are availabe for public view
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Abstract
Neurogenesis is regulated by environmental stimuli, stress and sex hormones which are factors that have been implicated in the pathophysiology of psychiatric disturbances. This led to a series of studies examining the effects of psychotropic drugs on neurogenesis. The results of these studies are interesting and suggest that regulation of neurogenesis could contribute to the therapeutic effects of different classes of psychotropic drugs.
The aim of the present study is to assess the neurogenesis effects of risperidone and its active metabolite paliperidone in the prefrontal cortex and the hippocampus of rats exposed to chronic restraint stress for 21 days. The rats were divided into 4 main groups, group Ⅰis the control, non stressed, non medicated rats, groupⅡis control rats exposed to chronic restraint stress, group Ⅲ is subdivided into 3 subgroups receiving risperidone in the doses (0.63, 1.25, 2.5 mg/kg/day) during exposure to chronic restraint stress and group Ⅳwhich is subdivided into 3 subgroups receiving paliperidone in the doses (0.63, 1.25, 2.5 mg/kg/day) during exposure to chronic restraint stress.
The following parameters were measured after 21 days:
1- serum corticosterone in rats as an indicator for induction of stress.
2- BDNF level in the prefrontal cortex and hippocampus of rats as a marker of neurogenesis.
In addition, histological and immunohistochemical studies of the prefrontal cortex and the hippocampus were done to assess the changes in the cellular number, morphology and viability in addition to the apoptotic changes.
The results showed the following:
1- Serum corticosterone level
- It was found that chronic restraint stress produced statistically significant (p<0.05) increase of the serum corticosterone concentration in rats compared with the control group.
- Concomitant administration of risperidone with restraint stress produced statistically significant (p<0.05) decrease of the serum corticosterone level in rats compared with the stressed non treated group with the doses 0.63 and 2.5 mg/kg/day.
- Paliperidone administration produced statistically significant (p<0.05) decrease of the serum corticosterone level in rats compared with the stressed non treated group.
2-BDNF level in the prefrontal cortex and hippocampus:
- BDNF concentration in the prefrontal cortex of rats exposed to 21 days restraint stress showed statistically insignificant (P>0.05) difference from the control group, while in the hippocampi it showed statistically significant (p<0.05) reduction compared with the control group.
- Risperidone administration to rats exposed to chronic restraint stress produced a statistically significant (p<0.05) increase of the BDNF concentration in the prefrontal cortex and the hippocampus compared with both control and stressed non-treated group.
- Paliperidone administration to rats exposed to chronic restraint stress produced a statistically insignificant (P>0.05) increase of the BDNF concentration in the prefrontal cortex compared with the stressed non-treated group, while it is statistically significant (p<0.05) increased the BDNF level in the rat hippocampi.
3- Histological and immunohistochemical study:
- Histological and immunohistochemical examination of the prefrontal cortex and the hippocampus of the rats exposed to 21 days restraint stress showed many degenerated and apoptotic cells in most of the layers with decrease in the Nissl’s granules and mitochondrial content in the cytoplasm compared with the control group.
- In risperidone treated groups, many cells in the prefrontal cortex appeared similar to that in the control group with some degenerated cells. There was increase in Nissl’s granules and mitochondria in the cytoplasm compared with the stressed non treated group with few apoptotic cells. While the hippocampus of the risperidone treated rats revealed apparent increase in pyramidal cell number than the stressed non treated group yet they appeared less tightly packed than those of the control group. Many cells appeared degenerated and few cells were healthy with vesicular nuclei. Apparent increase in Nissl’s granules and mitochondrial content was observed in the cytoplasm of the pyramidal cells than that of the stressed non treated group with some apoptotic cells.
- In the paliperidone treated group histological and immunohistochemical study of the prefrontal cortex revealed that many cells appeared similar to the control configuration, while there were some degenerated cells. There was increase in Nissl’s granules and mitochondria in the cytoplasm compared with the stressed non treated group. Immunohistochemical study showed few apoptotic cells. While the hippocampus showed that the pyramidal cells appeared crowded than the stressed non-treated group yet many cells appeared degenerated. Apparent increase in Nissl’s granules and mitochondrial content was observed in the cytoplasm of the pyramidal cells than that of the stressed non treated group. The immunohistochemical study showed some apoptotic cells.
Conclusion
The results of the present work provide an evidence for potential neurogenesis effect of risperidone and its active metabolite paliperidone which might add benefits to their therapeutic value in treatment of psychotic disorders.