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

The effects that chronic cocaine administration CCA have on craving, cocaine metabolite concentrations and cytochrome P450 3A4 isoenzyme CYP450 3A4 activities in Sprague-Dawley rats following the administration of Salako Nutritional Supplements SNS were examined. Five groups of fifty rats were used to assess the effect of the SNS following CCA. Craving was analyzed for each rat using a Conditioned Place Preference protocol. Blood samples were obtained at regular intervals and used to measure cocaine plasma metabolite levels. CYP450 3A4 activity was determined in the liver. Administration of the SNS reduced craving of cocaine significantly, upon discontinuing cocaine in the rats. Blood plasma analysis showing higher benzoylecgonine equilibrium and the CYP450 3A4 levels demonstrated that the SNS possibly aided in the removal of the stored metabolites indicative of increased metabolism of cocaine, enhanced by the Supplements. Results indicate that the SNS formulation reduces craving caused by CCA by increasing the liver CYP450 3A4 activity, resulting in better plasma clearance.

[1]  O. Pelkonen,et al.  The role of CYP enzymes in cocaine-induced liver damage , 2009, Archives of Toxicology.

[2]  S. Levine,et al.  Cerebrovascular complications of the use of the "crack" form of alkaloidal cocaine. , 1990, The New England journal of medicine.

[3]  D. Petersen,et al.  Hepatic biochemical changes as a result of acute cocaine administration in the mouse , 1991, Hepatology.

[4]  Gerra Gilberto,et al.  Dr. Gilberto Gerra, Chief of Drug Prevention and Health Branch, Division for Operations, United Nations Office on Drugs and Crime (UNODC), Vienna. , 2013 .

[5]  R. Bevins,et al.  Conditioned place preference: what does it add to our preclinical understanding of drug reward? , 2000, Psychopharmacology.

[6]  R. Maldonado,et al.  Cannabinoid Addiction: Behavioral Models and Neural Correlates , 2002, The Journal of Neuroscience.

[7]  R. Harbison,et al.  The Perturbation of Hepatic Glutathione by α2-Adrenergic Agonists , 1983 .

[8]  R. G. Bartlett,et al.  Relationship of adrenalin to tissue sulfhydryl compounds. , 1954, Science.

[9]  R. Bloch,et al.  Estimation and disposition of [3H]benzoylecgonine and pharmacological activity of some cocaine metabolites , 1975, The Journal of pharmacy and pharmacology.

[10]  C. Kilts,et al.  A controlled trial of the adjunct use of D-cycloserine to facilitate cognitive behavioral therapy outcomes in a cocaine-dependent population. , 2012, Addictive behaviors.

[11]  S. Hall,et al.  Superior efficacy of cognitive-behavioral therapy for urban crack cocaine abusers: main and matching effects. , 1998, Journal of consulting and clinical psychology.

[12]  J. Calabrese,et al.  Does recovery from substance use disorder matter in patients with bipolar disorder? , 2005, The Journal of clinical psychiatry.

[13]  T. Tzschentke,et al.  Measuring reward with the conditioned place preference paradigm: a comprehensive review of drug effects, recent progress and new issues , 1998, Progress in Neurobiology.

[14]  L. Shuster,et al.  Metabolism of cocaine and norcocaine to N-hydroxynorcocaine. , 1983, Biochemical pharmacology.

[15]  D. Murphy,et al.  Cocaine reward models: conditioned place preference can be established in dopamine- and in serotonin-transporter knockout mice. , 1998, Proceedings of the National Academy of Sciences of the United States of America.

[16]  Hawks Rl,et al.  Implications of drug levels in body fluids: basic concepts. , 1986 .

[17]  Jos H Beijnen,et al.  Pharmacokinetics and pharmacokinetic variability of heroin and its metabolites: review of the literature. , 2006, Current clinical pharmacology.

[18]  J. Wasserberger,et al.  Crack cocaine causing fatal vasoconstriction of the aorta. , 2006, The Journal of emergency medicine.

[19]  M. Centrone,et al.  Validation of an extraction and gas chromatography-mass spectrometry quantification method for cocaine, methadone, and morphine in postmortem adipose tissue. , 2010, Journal of analytical toxicology.

[20]  S. Higgins,et al.  Effects of voucher-based intervention on abstinence and retention in an outpatient treatment for cocaine addiction: a randomized controlled trial. , 2009, Experimental and clinical psychopharmacology.

[21]  G. Kanel,et al.  Cocaine‐induced liver cell injury: Comparison of morphological features in man and in experimental models , 1990, Hepatology.

[22]  K. Fuxe,et al.  LC/MS/MS evaluation of cocaine and its metabolites in different brain areas, peripheral organs and plasma in cocaine self-administering rats , 2012, Pharmacological reports : PR.

[23]  A T McLellan,et al.  Substance Abuse Treatment , 2011 .

[24]  M. Parmentier,et al.  Cocaine, but not morphine, induces conditioned place preference and sensitization to locomotor responses in CB1 knockout mice , 2000, The European journal of neuroscience.

[25]  M. Abdel‐Rahman,et al.  Effect of alcohol and/or cocaine on blood glutathione and the ultrastructure of the liver of pregnant CF-1 mice. , 1998, Toxicology letters.

[26]  N. Zahniser,et al.  Mechanisms of acute cocaine toxicity. , 2008, The open pharmacology journal.

[27]  I. Kopin,et al.  Norcocaine: a pharmacologically active metabolite of cocaine found in brain. , 1974, Life sciences.

[28]  L. Shuster,et al.  Cocaine-induced hepatic necrosis in mice--the role of cocaine metabolism. , 1979, Biochemical pharmacology.

[29]  Xiu-Ti Hu,et al.  Cocaine withdrawal and neuro-adaptations in ion channel function , 2007, Molecular Neurobiology.

[30]  Peter A. Groblewski,et al.  Drug-induced conditioned place preference and aversion in mice , 2006, Nature Protocols.

[31]  E. Carboni,et al.  Conditioned Place Preference , 2003 .

[32]  L. Espinoza,et al.  Cocaine-Induced Vasculitis: Clinical and Immunological Spectrum , 2012, Current Rheumatology Reports.