Reinforcement cocaine dependence

Higgins ST, Sigmon SC, Wong CJ, et al Community reinforcement therapy for cocaine-dependent outpatients. Arch Gen Psychiatry 60 1043—1052, 2003 Hopkins JS, Garbutt JC, Poole CL, et al Naltrexone and acamprosate meta-analysis of two medical treatments for alcoholism. Presented at the 25th annual meeting of the Research Society on Alcoholism, San Francisco, CA, June 28—July 3, 2002... 

An alternative pharmacotherapy for cocaine dependence currently under investigation is use of a cocaine vaccine to blunt the reinforcing effects of cocaine.51 60 The basis of this pharmacotherapy is to decrease the rate of entry of cocaine into the CNS (and therefore the onset of action), by either binding cocaine with antibody generated by active immunization with a stable cocaine conjugate or by using an enzymatically active antibody specific for cocaine. 

The search for an agent to treat cocaine addiction, one that would not produce euphoria but would still prevent withdrawal, is currently under way. Unfortunately, to date, cocaine dependence has proved to be highly resistant to therapy, primarily because of its powerful reinforcing potency. Recently, however, animal studies have produced what may be a new direction in treating cocaine addiction. As described... 

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. 

Dependence and withdrawal can occur with all of the stimulants. Cocaine is one of the most strongly reinforcing drugs in self-administration paradigms in animals and also has a psychological withdrawal syndrome. A typical pattern of withdrawal includes a ravenous appetite, exhaustion, and mental depression, which may last for several days after the drug is withdrawn. Because tolerance develops quickly, abusers may take large doses, compared with those used medically, for example, as anorexiants. 

A number of psychosocial treatments for alcohol and other substance use disorders exist and are widely used. In this chapter, we discuss six of these psychotherapies as they are applied to alcohol, cocaine, and opioid dependence brief interventions, motivational enhancement therapy, cognitive-behavioral therapy, behavioral treatments (including contingency management and community reinforcement approaches), behavioral marital therapy, and 12-step facilitation. We also describe studies that examined the efficacy of a medication in combination with one or more of the six psychotherapies. In the second section of the chapter, we highlight research that directly studied the interaction between psychosocial and pharmacological treatments. 

Carroll KM, Sinha R, Nich C, er al Conringency management to enhance naltrexone treatment of opioid dependence a randomized clinical trial of reinforcement magnitude. Exp Clin Psychopharmacol 10 5d—63, 2002 Carroll KM, Fenron LR, Ball SA, er al Efficacy of disulfiram and cognitive behavior rherapy in cocaine-dependenr ourparienrs. Arch Gen Psychiatry 61 264—272, 2004... 

Schottenfeld RS, Chawarski MC, Pakes JR, et al Methadone versus buprenorphine with contingency management or performance feedback for cocaine and opioid dependence. Am J Psychiatry 162 340-349, 2003 Smith JE, Meyers RJ, Delaney HD Community reinforcement approach with homeless alcohol-dependent individuals. J Consult Clin Psychol 66 341-348, 1998... 

Studies in knockout mice indicate that the p2 nAChRs are necessary for nicotine self-administration, DA-dependent locomotor activation, and nicotine-associated enhancement of NAc DA release.40-51 53 Combined with studies showing that antagonism of the high-affinity nAChRs block self-administration,44-54 it would appear that p2 nAChRs are particularly critical for nicotine reinforcement. Unlike wild-type mice that self-administer both cocaine and nicotine, p2 nAChR-null mutant mice learn to self-administer cocaine normally, but stop bar pressing as though receiving saline when cocaine is switched to nicotine.40 Self-administration of VTA nicotine and associated DA release is rescued, however, in p2 nAChR knockout mice with lentiviral-mediated expression of P2 subunit DNA in the VTA.55 Whereas several configurations of the p2 nAChRs exist at the... 

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