Investigation of the antinociceptive and antiinflammatory effects of risperidone by in vivo methods

Risperidone is an atypical antipsychotic that potently blocks D2 dopaminergic and 5-HT2 serotonergic receptors. Based on the roles of dopaminergic and serotonergic systems in the transmission and modulation of pain and previous studies pointing out the potential efficacy of risperidone on pain and inflammation, it was aimed to investigate antinociceptive and anti-inflammatory effect of risperidone, in this thesis study. The antinociceptive efficacy of risperidone (0.05, 0.1 and 0.2 mg.kg-1) on thermal nociceptive stimuli was evaluated by hot-plate and tail immersion whereas antinociceptive efficacy of this drug on mechanical nociceptive stimuli was examined by tail-clip tests. Risperidone did not show significant antinociceptive activity in any of these tests. These findings revealed that this drug does not have a central mechanism-mediated antinociceptive effect against pain induced by thermal or mechanical nociceptive stimuli. On the other hand, in the acetic acid-induced writhing test, at all three doses, risperidone showed antinociceptive activity on neuronal pathways carrying chemical nociceptive stimuli by significantly reducing the number of writhing behaviors. The mechanistic studies indicated that antinociceptive activity of risperidone is related to the glutamatergic system and sGMP/ATP-sensitive K+ channels. Risperidone, at the same doses, also showed anti-inflammatory activity by significantly reducing carrageenan-induced paw edema in rats. More comprehensive studies, in which the possible effects of this drug on pain- and inflammation-related endogenous mediators, enzymes and receptors examined by in vivo and in vitro methods, are needed in order to elucidate precise mechanism of the risperidone-induced antinociceptive and anti-inflammatory effects, which were presented for the first time in this study. Keywords: Pain, Inflammation, Nociception, Risperidone.