An investigation into the neurochemical and behavioural patterns of C57Bl6 mice exposed to "Sugars" and its constituents.

Abstract

“Sugars” is an illicit drug cocktail that is a low-grade mixture of heroin and other opioids. The composition of this cocktail is highly varied as other ingredients are added during its manufacturing process to add bulk to the mixture and possibly increase profits of the suppliers. This highly addictive cocktail requires only a single use to initiate dependence and if not used timeously thereafter, severe withdrawal symptoms occur as soon as four hours after the last use. Due to the highly variable composition of this drug cocktail, it has been difficult to create a rehabilitation program with a low relapse rate as the physiological mechanisms of action of this cocktail have not been previously investigated. This study therefore aimed to investigate the physiological effects of “Sugars” and its ingredients in an animal model. This would provide novel findings on the pharmacological actions of the components of “Sugars” in the body as well as the physiological changes that may result during administration and withdrawal of the drug. This thesis is comprised of four manuscripts viz. one review paper that discusses the psychosocial issues of “Sugars” from an ethnographic standpoint and three experimental papers that focus on neurophysiology, behaviour, and immunology. The first experimental paper focuses on dopamine concentrations which were analysed using an ELISA assay and the sucrose preference test which can be used to assess the anhedonic behaviour in an animal model. The second paper focuses on the changes in memory function which was assessed using the Morris water maze and hippocampal mass and the third paper discusses changes in circulating immune cells following the analysis of blood samples with a heamotology analyser . The major findings emanating from this study were that administration of “Sugars” resulted in substantial changes in the dopaminergic system, cognitive abilities and haematological parameters involved in immunity; however, it was also observed that these changes were potentially reversed following a withdrawal period of 10 days in a mouse model. The extent of the effects observed may have also been influenced by the ratio of the ingredients in the cocktail. These novel findings can therefore assist in the formation of a targeted rehabilitation program that factors in the changes in the various physiological systems as discussed in this thesis. Key words: “Sugars”, illicit drug cocktail, dopamine, heroin, hippocampus