Dopamine cocaine dependence

Somoza EC, Winhusen TM, Bridge TP, et al An open-label pilot study of methylpheni-date in the treatment of cocaine-dependent patients with adult attention deficit/ hyperactivity disorder. J Addict Dis 23 77—92, 2004 Sora 1, Wichems C, Takahashi N, et al Cocaine reward models conditioned place preference can be established in dopamine- and in serotonin-transporter knockout mice. Proc Natl Acad Sci U S A 95 7699-7704, 1998 Soral, Hall FS, Andrews AM, etal Molecular mechanisms of cocaine reward combined dopamine and serotonin transporter knockouts eliminate cocaine place preference. Proc Nad Acad Sci U S A 98 5300-5305, 2001 Spear J, Alderton D Psychosis associated with prescribed dexamphetamine use 0etter). 

There are no proven pharmacotherapies for treatment of cocaine or amphetamine dependence. Disulfiram, however, shows some promise in randomized controlled trials for treating cocaine dependence at doses of 250 mg daily, especially in combination with CBT.45 Its mechanism of action for treating cocaine dependence is not known, but may be due to its inhibition of the dopamine P-hydroxylase enzyme that converts DA to NE in the brain. The resulting increase in DA levels may counter the DA-deficient state that is believed to underlie cocaine withdrawal and craving. 

DA TRANSPORTER AND COCAINE DEPENDENCE 5.2.1 Regulation of the Dopamine Transporter (DAT) by Cocaine... 

Gelernter, J., Kranzler, H., and Satel, S.L. (1999b) No association between D2 dopamine receptor (DRD2) alleles or haplotypes and cocaine dependence or severity of cocaine dependence in European- and African-Americans. Biol Psychiatry 45 340— 345. 

Dopamine agonists, including the stimulants, have been used as substitution agents in cocaine-dependent adults, but with little success (Kranzler et al., 1999). For example, one controlled study has found that stim-... 

Soares B, Limas M, Reisser A Farrell M (2003). Dopamine agonists for cocaine dependence... 

Noble, Ernest P., Kenneth Blum, M. E. Khalsa, Terry Ritchie, Anne Montgomery, R. C. Wood, R. J. Fitch, T. Ozkaragoz, Peter J. Sheridan, M. D. Anglin, A. Paredes, L. J. Treiman, and R. S. Sparks. 1993. "Allelic Association of the D2 Dopamine Receptor Gene with Cocaine Dependence." Drug and Alcohol Dependence 33 271-85. 

The possible genetic basis of cocaine-induced paranoia has been studied in 45 European Americans with cocaine dependency (181). Low activity of the enzyme dopamine P-hydroxylase (the enzyme that catalyses the conversion of dopamine to noradrenaline) in the serum or cerebrospinal fluid was positively associated with the occurrence of positive psychotic symptoms in several psychiatric disorders. The activity of dopamine P-hydroxylase is a stable, genetically determined trait that is regulated by genes located at the DBH locus. The haplotype associated with low dopamine P-hydroxylase activity, Del-a, occurred more often in 29 subjects with cocaine-induced paranoia than in 16 without. These findings may have implications for the pharmacological treatment of cocaine dependence. 

Reith, 1988), and the extensive literature which suggests that cocaine s reinforcing effects are mediated by increases in extracellular dopamine levels in the mesolim-bic dopamine system (Ritz et al., 1987 Koob and Bloom, 1988 Johanson and Fischman, 1989 Kuhar et al., 1991 Woolverton and Johnson, 1992). Dopamine receptor antagonists have been evaluated for their potential utility in treating cocaine abuse (Mello and Negus, 1996) but such agents produce extrapyramidal motor effects and other unwanted effects that complicate their use in the treatment of cocaine dependence. 

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