P.1.g.062 The new nociceptin analogue PheGlyGlyPheValGlyPro: dose-dependent effects on pain sensitivity and locomotor activity in rat

Abstract

antipsychotic (extended-release paliperidone palmitate). The study has been approved by the Ethical Committee of the University of Medicine and Pharmacy of Craiova and was conducted according to ethical regulations for the research on animals. Method: We have studied on Wistar rats the neuroprotective effects of the two long-acting antipsychotics (haloperidol decanoate vs. paliperidone palmitate) against a control group (N0) during 14 days. The study groups included 8 adult, male rats with weight between 200 and 250 grams. They were kept during the entire study in a stress-free environment with optimal parameters of temperature, humidity and food. The substances were administered in intramuscular injections on Day 0: group N1 − haloperidol decanoate (0.5mg/kg), group N2 − paliperidone palmitate (0.5mg/kg) and control group N0 − saline solution. During the 14 days of the study, the subjects were monitored for extrapyramidal signs and behavioral changes. The rats were sacrificed on Day 15 and biological material from the frontal cortex and hippocampus was prepared with specific histological techniques of coloration and fixation: hematoxyline-eosine, trichromicGS, PAShematoxyline, toluidine blue, methylen blue for Nissle corpuscles. Results: The observations during the 14 days revealed extrapyramidal manifestations of medium intensity only within group N1 and avoidant behavior more obvious in group N1 compared with group N2. The assessment of neuroprotection employed optical microscopy and involved the cytoarchitecture of the frontal cortex, dentate gyrus and hippocampus. The histological studies showed significant changes in group N1 (haloperidol decanoate) with large neuronal losses in the layers I, II and III of the frontal cortex, areas of intense vacuoliosation and picnocytosis, as well as microbleedings and vessels of neoformation. In group N2, the changes in frontal cortex were minimal with only a few areas of vacuolisation and vessels of neoformation. The hippocampal area was significantly destructured in group N1, with an evident loss of neural interconnects in area CA1CA3, as well as microbleedings in the dentate gyrus. Many hippocampal structures were affected by picnocytosis to the level of complete neuronal destruction. Changes induced by paliperidone at hippocampal level were also minimal, without picnocytosis or neuronal destruction. Conclusions: On animal mode, haloperidol decanoate demonstrates a significant loss of neuroprotection compared with paliperidone palmitate, as most vulnerable areas are the frontal cortex and hippocampus with close correlation with a possible disturbance of the cortical-subcortical circuits. The new longacting antipsychotic, paliperidone palmitate, suggests the premises of a superior neuroprotection.