Further evidence for the involvement of 5-HT2C receptors in the pentylenetetrazole model of epilepsy

Abstract

To clarify the role of 5-HT2C receptors in the generation of epilepsy this study investigated the effects of the 5-HT2C receptor-preferring agonist 1-(m-chlorophenyl)-piperazine (mCPP) and the subtype-selective 5-HT2C receptor antagonist SB 242084 in pentylenetetrazole (PTZ)-evoked seizures in mice. All drugs were given subcutaneously (s.c.) 60 minutes before PTZ injection (100 mg/kg s.c.). The seizure patterns were recorded during a 60 min period following the injection of PTZ. The following parameters were evaluated: survival rate, duration of survival, seizure latency, seizure level (from 0 to 4) and seizure duration. The activity score for each mouse was defined as the seizure duration time-weighted average of the seizure levels. The significance of the survival rate was assessed by the Chi-square test, for the other parameters we applied oneway ANOVA. mCPP (1, 5 and 25 mg/kg s.c.) significantly increased the rate and the duration of survival and changed the pattern of seizure levels. These effects followed a bell-shaped dose-response curve and were completely abolished by 5 mg/kg of SB 242084, although the antagonist alone did not modify the seizure parameters. These results indicate that the anticonvulsant effects of mCPP might be mediated by activation of 5-HT2C receptors. However, the lack of the effect of the selective antagonist SB 242084 (1, 2.5 and 5 mg/kg s.c.) on the seizure parameters suggests that the function of this 5-HT receptor subtype depends on the level of 5-HT tone. from 13th Scientific Symposium of the Austrian Pharmacological Society (APHAR). Joint Meeting with the Austrian Society of Toxicology (ASTOX) and the Hungarian Society for Experimental and Clinical Pharmacology (MFT) Vienna, Austria. 22–24 November 2007