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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
vii
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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