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

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

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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

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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.

CHAPTER ONE

1.0    Introduction

1.1 Background of the Study

Addiction is a chronic, relapsing brain disease characterized by compulsive drug-seeking

and use, despite harmful consequences to the individual and society (Koob and Volkow,

2010). The disease affects both the brain and behaviour. It is considered a brain disease

because drugs causing addiction also change the structure and function of the brain (Alan

1997). The brain changes may be long-lasting, causing harmful behaviours seen in people

who abuse drugs. People of all ages suffer the harmful consequences of drug abuse and

addiction. The national institute on drug abuse in 2008 estimated 2.1 million Americans

aged 12 and older had abused 3,4-Methylenedioxymethamphetamine (MDMA) at least

once in their life. Over 32 million people or almost 10% of the adult population in the

European Union used the drug in 2008, according to the annual report of the European

Monitoring Center for Drugs and Drug Addiction (EMCDDA). Around 2 million drug

users in Europe preferred amphetamine while ecstasy was used by 2.5 million people.

Approximately 12 million have tried amphetamine and 10 million have tried ecstasy at

least once in their lives. The use of ecstasy is overtaking the other amphetamines and

getting the second place after cannabis, in both general population and school surveys

approximately represent 22% of total drug abusers (EMCDDA 2008).


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