EVALUATION OF CO-ADMINISTRATION OF ETHYL ACETATE FRACTION OF Cannabis sativa LEAVES AND ETHANOL ON LEARNING, MEMORY AND THE HISTOMORPHOLOGY OF THE HIPPOCAMPUS IN MICE (Mus musculus)

EVALUATION OF CO-ADMINISTRATION OF ETHYL ACETATE FRACTION OF Cannabis sativa LEAVES AND ETHANOL ON LEARNING, MEMORY AND THE HISTOMORPHOLOGY OF THE HIPPOCAMPUS IN MICE (Mus musculus)

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ABSTRACT

Substance abuse especially amongst young adults constitutes a global problem. Cannabis sativa is a commonly abused illicit drug. Some of its effects include impaired short memory, attention and reduced motor skills. Ethanol is a multiple action depressor of the central nervous system and under its influence, confused and disorganized thinking results. Both drugs have a detrimental effect on prospective memory in adults but users may not be aware of this. This study was therefore aimed at evaluating the co-administration of ethyl acetate fraction of Cannabis sativa leaves and ethanol on Learning, Memory and the histomorphology of the Hippocampus in Mice (Mus Musculus) using the Y-maze and Novel Object Recognition (NOR) paradigms. Fourty eight apparently healthy male albino mice of 20-28 g body weight were assigned into two major groups consisting of four sub-groups each; A, B, C, and D. Each sub group had six mice each (n=6). Sub-groups A, B, C, and D were administered distilled water 1 ml/kg body weight (bwt) (control), 145 mg/kg bwt ethyl acetate fraction of Cannabis sativa leaves, ethanol 20% v/kg bwt and co-administration of 145 mg/kg bwt ethyl acetate fraction of Cannabis sativa leaves and 20% v/kg bwt of alcohol respectively, orally for 21 days. Neurobehavioural assessment was carried out using the Y-maze and Novel Object Recognition (NOR) Paradigms. The Hippocampal histology and volumes were obtained using H & E staining technique and Cavalieri estimator respectively. Data were expressed as mean±SEM. One way ANOVA and Kruskal Wallis tests were used to compare the means at p<0.05. The result of Y-maze test showed a significant increase (P<0.05) in the mean rank of the co-administered group followed by the cannabis group indicating memory impairment when compared to control. NORT result showed a significant decrease (P<0.05) in discrimination and retention indexes in the co-administered group followed by the Cannabis sativa treated group when compared to control. A non-statistical significant (P>0.05) decrease was observed in Hippocampal volume when compared to the control. Histopathological evaluation revealed disorganization and focal necrosis of pyramidal cells of the hippocampus in the co-administered group when compared to the control. It can therefore be inferred from the findings of this study that, co-administration of ethyl acetate fraction of Cannabis sativa leaves with ethanol is more detrimental to hippocampal histoarchitecture with a corresponding memory impairment relative to administration of either.

CHAPTER ONE

1.0 INTRODUCTION

Substance abuse, also known as drug abuse, is a patterned use of a drug in which the user

consumes the substance in amounts or with methods which are harmful to themselves or others,

and is a form of substance-related disorder (Kris and Oakley Ray, 2002). Widely differing

definitions of drug abuse are used in public health, medical and criminal justice contexts. In

some cases criminal or anti-social behavior occurs when the person is under the influence of a

drug, and long term personality changes in individuals may occur as well (Kris and Oakley Ray,

2002). Cannabis sativa and alcohol are among the most commonly abused illicit drugs (Fontes et

al., 2011).

Cannabis sativa, commonly known as marijuana (prepared leaves), is one of the most commonly

used illicit drugs for recreational purposes. Cannabis sativa contains a unique group of chemicals

called cannabinoids. Its main psychoactive constituent is tetrahydro cannabinol (THC). The plant

is known to contain about sixty cannabinoids; however, most of these „minor‟ cannabinoids are

only produced in trace amounts (Ashton, 2001). The psychoactive substance in cannabis, delta-9-

tetrahydrocannabinol (THC), stimulates cannabinoid receptors (CBRs), located on the surface of

neurons, to produce the psychoactive effects.

Alcohol is also a psychoactive substance based on its abilities to alter human consciousness. It is

commonly consumed as a recreational drug. It also acts as „gateway‟ drug to the use of other

substances like cocaine, heroin, amphetamine, inhalants and hallucinogens (Makanjuola et al,

2014). Alcohol has effects on every organ in the drinker's body. Intoxication can impair brain

function and motor skills; chronic use can increase risk of cancers, stroke, and liver disease.

Alcoholism or alcohol dependence is a diagnosable disease characterized by a strong craving for

1


alcohol, with continued use despite harm or injury. Alcohol abuse is a pattern of drinking that

result in harm to one's health, interpersonal relationships, or ability to work (NIDA, 2015).

1.2       Statement of Research Problem


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