Plasma Cocaine Metabolite and Liver CYP450 3A4 Isoenzyme Levels as Indicators of Cocaine Dependence in Rats Treated with Nutritional Supplements

Metabolism of Cocaine

Cocaine is rapidly absorbed in the blood following the snorting, smoking and intravenous administration. Cocaine is metabolized by several enzymatic and non-enzymatic pathways (Heard et al., 2008) rapidly and extensively in animals to yield benzoylecgonine and ecgonine as the principal products, along with other metabolites, particularly ecgonine methyl ester, which are all generally inactive. Norcocaine is a minor metabolite that is formed, but is active and found to be neurotoxic. Cocaine is converted to norcocaine via the cytochrome P450 3A4 isoenzyme by means of N-demethylation. Norcocaine has shown to be equal in potency to cocaine (Hawks et al., 1974; Misra et al., 1975). The pharmacology of cocaine is complex, which exhibits simultaneous effects in several organ systems in the body including the brain, cardiovascular, immune and hematological systems (Espinoza, 2012; Heard et al., 2008 and Levine et al., 1990). Cocaine has been shown to be extremely hepatotoxic (Boyer & Peterson, 2005; Kanel et al., 1989; Pasanen et al., 1995) and also results in fatty infiltration responsible for increases in lipid content of the liver (Affi et al., 1998; MachLachlan & Hodge, 1938). Developing an effective, safe and cost-effective means of treating substance abuse is of paramount importance in society.

Chronic use of cocaine results in the metabolite being present in the urine for a prolonged period following introduction of a large amount into the body. There is still a paucity of information which exists regarding the effects that cocaine has on the body as a complete system, including the toxicity that exists during chronic usage and the general basic mode of action following varying modes of administration.

Conditioned Place Preference

Conditioned place preference is one popular method of an animal model of drug dependence. The apparatus used to carry out the experiment is called a conditioned place preference box, which consists of two chambers separated by a neutral chamber. One chamber differs from the other by tactile clues such as colour and light intensity. Using a biased procedure, the non-preferred compartment is paired with the drug and the CPP is a measurement of overcoming the initial aversion for that compartment (Sanchis-Segura and Spanagel, 2006). In adult rats, place preference for cocaine is effectively established for cocaine at a dosage of 20 mg/kg (Bardo et al. 1986; and Brenhouse and Andersen, 2008).