EFFECT OF AMBIENT TEMPERATURE ON METHYLENEDIOXYMETHAMPHETAMINE (MDMA)-INDUCED CHANGES IN BODY TEMPERATURE, NEUROBEHAVIOUR AND NEUROTOXICITY IN RODENTS

By

Author

Presented To

Department of Medicine

ABSTRACT
Studies on the effect of ambient temperature on methylenedioxymethamphetamine (MDMA)-induced changes in body temperature, neurobehaviour and neurotoxicity was carried out in mice and rats. The study was carried out in four (4) different categories and designed to determine variations in ambient temperature on MDMA-induced changes on body temperature, neurobehaviour and neurotoxicity. Category 1, made up of twenty male C57BL/6J mice were grouped into four groups of 5 each (n=5). Group 1a (control: normal saline and Temperature of 21°C), group IIa (Temperature of 21°C and MDMA (4 x 20 mg/kg). Group Ib (control: normal saline and Temperature of 27°C), group 11b (Temperature of 27°C and MDMA (4 x 20 mg/kg). Core body temperature was measured each hour after each vehicle or MDMA administration. Category 2, mice were sacrificed 48 hrs after the last administration of MDMA and coronary striatal sections were used for neurotoxicity analysis with glial fibrilliary acidic protein (GFAP) and CD 11b as markers of astroglia and microglia. Category 3, assessment of short-term spatial memory using Y-maze in rats and divided into four groups of 10 each (n=10). Groups 1a and 1b served as control and were given normal saline and kept at an environmental temperatures of 21°C and 27°C respectively. Groups IIa and 11b were administered MDMA (10 mg/kg) and kept at an environmental temperatures of 21°C and 27°C respectively. Category 4, assessment of non-spatial working memory using novel object recognition task in rats grouped into four groups of 10 each (n=10). Groups 1a and 1b served as control and were given normal saline and kept at an environmental temperatures of 21°C and 27°C respectively. Groups IIa and 11b were administered MDMA (10 mg/kg) and kept at an environmental temperatures of 21°C and 27°C respectively. All administrations were i.p. 24 hrs apart over four consecutive days. The results showed that body temperature of MDMA-treated mice was significantly higher (p<0.05) than mice treated with vehicle at 21°C. Similarly, body temperature of MDMA-treated mice was significantly higher (p<0.05) than mice treated with vehicle at the 27°C. The body temperature of MDMA-treated mice at 27°C was significantly higher (p<0.05) than mice treated at 21°C. Mice exposed to 21°C and 27°C, MDMA-treated mice showed a higher CD 11b immunoreactivity (microgliosis) was observed as compared with vehicle- treated mice. Mice treated at 27°C showed a higher CD 11b immunoreactivity compared with mice treated at 21°C. Exposure to 21°C and 27°C, MDMA induced a significantly higher GFAP (p<0.05) immunoreactivity (Astrogliosis) compared with vehicle treated mice. MDMA-treated mice at 27oC showed a significantly higher (p<0.05) GFAP immunoreactivity compared with mice exposed at 21°C. At 21°C and 27°C there was a significant (p<0.001) impairemant in both spatial and non-spatial memory in MDMA-treated rats as compared to the vehicle treated. Impairment in spatial and non-spatial memory in MDMA-treated rats at 27°C was significantly higher than in MDMA-treated rats at 21°C (p<0.001). In conclusion, MDMA induced hyperthermia, neurotoxicity and impairement in both spatial and non-spatial memory depending on variations in ambient temperature.