Summary

Dependence and addiction are most appropriately understood as chronic medical disorders, with frequent recurrences to be expected. The neurobiology of these disorders is becoming well understood, but much remains unknown about the genomic mechanisms that predispose to addictions and that are activated, perhaps irreversibly, by long-term drug use. The mesolimbic reward system appears to be central to the development of the direct clinical consequences of chronic abuse, including tolerance, dependence, and addiction. Other brain areas and neurochemicals, including cortisol, also are relevant to dependence and relapse. Pharmacological interventions for addiction are highly effective for opiates, and we have illustrated three different approaches using an agonist, an antagonist, or a partial agonist. However, given the complex biological, psycho logical, and social aspects of these diseases, they must be accompanied by appropriate psychosocial treatments. Clinician awareness of the neurobiologi-cal basis of drug dependence, and information sharing with patients, can provide insight into patient behaviors and problems, and clarify the rationale for treatment methods and goals.

ACKNOWLEDGMENT

This work was supported by Grant Nos. P50-DA-12762, K05-DA-00454, K12-DA-00167, R01-DA-13672, and R01-DA-14039 from the National Institute on Drug Abuse.

REFERENCES

Behar, K. L., Rothman, D. L., Petersen, K. F., Hooten, M., Delaney, R., Petroff, O. A., et al. (1999). Preliminary evidence of low cortical GABA levels in localized 1H-MR spectra of alcohol-dependent and hepatic encephalopathy patients. Am J Psychiatry, 156, 952-954.

Breiter, H. C., Gollub, R. L., Weisskoff, R. M., Kennedy, D. N., Makris, N., Berke, J. D., et al. (1997). Acute effects of cocaine on human brain activity and emotion. Neuron, 19, 591-611.

Fadda, F., & Rossetti, Z. L. (1998). Chronic ethanol consumption: From neuroadaptation to neurodegeneration. Prog Neurobiol, 56, 385-431.

Grace, A. A. (2000). The tonic/phasic model of dopamine system regulation and its implications for understanding alcohol and stimulant craving. Addiction, 95 (Suppl 2), S119-S128.

Kling, M. A., Carson, R. E., Borg, L., Zametkin, A., Matochik, J. A., Schluger, J., et al. (2000). Opioid receptor imaging with PET and [18F]cyclofoxy in long-term, methadone-treated former heroin addicts. J Pharmacol Exp Ther, 295, 1070-1076.

Koob, G. F., & LeMoal, M. (2001). Drug addiction, dysregulation of reward, and allostasis. Neuropsychopharmacology, 24, 97-129.

Kosten, T. R. (1990). Neurobiology of abused drugs: Opioids and stimulants. J Nerv Ment Dis, 178, 217-227.

Kosten, T. R. (1998). Pharmacotherapy of cerebral ischemia in cocaine dependence. Drug Alcohol Depend, 49, 133-144.

Kosten, T. R. (2000). Drugs of abuse (Chapter 32 revision). In G. B. Katzung (Ed.), Basic and clinical pharmacology (8th ed., pp. 532-547). Stamford, CT: Appleton & Lange.

Kosten, T. R. (2002). Pathophysiology and treatment of cocaine dependence. In K. L. Davis, D. Charney, J. T. Coyle, & C. Nemeroff (Eds.), Neuropsychopharmacology: The fifth generation of progress (pp. 1461-1473). Baltimore: Lippincott/Williams & Wilkins.

Kosten, T. R., & Kleber, H. D. (1984). Strategies to improve compliance with narcotic antagonists. Am J Drug Alcohol Abuse, 10, 249-266.

Kosten, T. R., & O'Connor, P. G. (2003). Current concepts—management of drug withdrawal. N Engl J Med, 348, 1786-1795.

Kosten, T. R., Schottenfeld, R. S., Ziedonis, D., & Falcioni, J. (1993). Buprenorphine versus methadone maintenance for opioid dependence. J Nerv Ment Dis, 181, 358364.

Kreek, M. J. (2000). Methadone-related opioid agonist pharmacotherapy for heroin addiction: History, recent molecular and neurochemical research and the future in mainstream medicine. Ann NY Acad Sci, 909, 186-216.

Kreek, M. J., & Koob, G. F. (1998). Drug dependence: Stress and dysregulation of brain reward pathways. Drug Alcohol Depend, 51(1-2), 23-47.

Nestler, E. J. (2002). From neurobiology to treatment: Progress against addiction. Nat Neurosci, 5(Suppl), 1076-1079.

Oliveto, A. H., Feingold, A., Schottenfeld, R., Jatlow, P., & Kosten, T. R. (1999). Desipramine in opioid-dependent cocaine abusers maintained on buprenorphine vs methadone. Arch Gen Psychiatry, 56, 812-820.

Raine, A., Lencz, T., Bihrle, S., LaCasse, L., & Colletti, P. (2000). Reduced prefrontal gray matter volume and reduced autonomic activity in antisocial personality disorder. Arch Gen Psychiatry, 57(2), 119-127.

Robinson, T. E., & Berridge, K. C. (2000). The psychology and neurobiology of addiction: An incentive-sensitization view. Addiction, 95(Suppl 2), S91-S117.

Schluger, J. H., Borg, L., Ho, A., & Kreek, M. J. (2001). Altered HPA axis responsivity to metyrapone testing in methadone maintained former heroin addicts with ongoing cocaine addiction. Neuropsychopharmacology, 24(5), 568-575.

Schottenfeld, R. S., Pakes, J. R., Oliveto, A., Ziedonis, D., & Kosten, T. R. (1997). Buprenorphine versus methadone maintenance treatment for concurrent opioid dependence and cocaine abuse. Arch Gen Psychiatry, 54(8), 713-720.

Shaham, Y., Erb, S., & Stewart, J. (2000). Stress-induced relapse to heroin and cocaine seeking in rats: A review. Brain Res Brain Res Rev, 33, 13-33.

Sinha, R., Catapano, D., & O'Malley, S. (1999). Stress-induced craving and stress response in cocaine dependent individuals. Psychopharmacology, 142, 343-351.

Stahl, S. M. (1998). Getting stoned without inhaling: Anandamide is the brain's natural marijuana. J Clin Psychiatry, 59, 566-567.

Stahl, S. M. (2002). Selective actions on sleep or anxiety by exploiting GABA-A/ benzodiazepine receptor subtypes. J Clin Psychiatry, 63, 179-180.

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