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GABA systems, benzodiazepines, and substance dependence.
J Clin Psychiatry. 2003; 64 Suppl 3:36-40.JC

Abstract

Alterations in the gamma-aminobutyric acid (GABA) receptor complex and GABA neurotransmission influence the reinforcing and intoxicating effects of alcohol and benzodiazepines. Chronic modulation of the GABA(A)-benzodiazepine receptor complex plays a major role in central nervous system dysregulation during alcohol abstinence. Withdrawal symptoms stem in part from a decreased GABAergic inhibitory function and an increase in glutamatergic excitatory function. GABA(A) receptors play a role in both reward and withdrawal phenomena from alcohol and sedative-hypnotics. Although less well understood, GABA(B) receptor complexes appear to play a role in inhibition of motivation and diminish relapse potential to reinforcing drugs. Evidence suggests that long-term alcohol use and concomitant serial withdrawals permanently alter GABAergic function, down-regulate benzodiazepine binding sites, and in preclinical models lead to cell death. Benzodiazepines have substantial drawbacks in the treatment of substance use-related disorders that include interactions with alcohol, rebound effects, alcohol priming, and the risk of supplanting alcohol dependency with addiction to both alcohol and benzodiazepines. Polysubstance-dependent individuals frequently self-medicate with benzodiazepines. Selective GABA agents with novel mechanisms of action have anxiolytic, anticonvulsant, and reward inhibition profiles that have potential in treating substance use and withdrawal and enhancing relapse prevention with less liability than benzodiazepines. The GABA(B) receptor agonist baclofen has promise in relapse prevention in a number of substance dependence disorders. The GABA(A) and GABA(B) pump reuptake inhibitor tiagabine has potential for managing alcohol and sedative-hypnotic withdrawal and also possibly a role in relapse prevention.

Authors+Show Affiliations

Medical University of South Carolina, Center for Drug and Alcohol Programs, Charleston 29425, USA.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

12662132

Citation

Malcolm, Robert J.. "GABA Systems, Benzodiazepines, and Substance Dependence." The Journal of Clinical Psychiatry, vol. 64 Suppl 3, 2003, pp. 36-40.
Malcolm RJ. GABA systems, benzodiazepines, and substance dependence. J Clin Psychiatry. 2003;64 Suppl 3:36-40.
Malcolm, R. J. (2003). GABA systems, benzodiazepines, and substance dependence. The Journal of Clinical Psychiatry, 64 Suppl 3, 36-40.
Malcolm RJ. GABA Systems, Benzodiazepines, and Substance Dependence. J Clin Psychiatry. 2003;64 Suppl 3:36-40. PubMed PMID: 12662132.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - GABA systems, benzodiazepines, and substance dependence. A1 - Malcolm,Robert J, PY - 2003/3/29/pubmed PY - 2003/4/23/medline PY - 2003/3/29/entrez SP - 36 EP - 40 JF - The Journal of clinical psychiatry JO - J Clin Psychiatry VL - 64 Suppl 3 N2 - Alterations in the gamma-aminobutyric acid (GABA) receptor complex and GABA neurotransmission influence the reinforcing and intoxicating effects of alcohol and benzodiazepines. Chronic modulation of the GABA(A)-benzodiazepine receptor complex plays a major role in central nervous system dysregulation during alcohol abstinence. Withdrawal symptoms stem in part from a decreased GABAergic inhibitory function and an increase in glutamatergic excitatory function. GABA(A) receptors play a role in both reward and withdrawal phenomena from alcohol and sedative-hypnotics. Although less well understood, GABA(B) receptor complexes appear to play a role in inhibition of motivation and diminish relapse potential to reinforcing drugs. Evidence suggests that long-term alcohol use and concomitant serial withdrawals permanently alter GABAergic function, down-regulate benzodiazepine binding sites, and in preclinical models lead to cell death. Benzodiazepines have substantial drawbacks in the treatment of substance use-related disorders that include interactions with alcohol, rebound effects, alcohol priming, and the risk of supplanting alcohol dependency with addiction to both alcohol and benzodiazepines. Polysubstance-dependent individuals frequently self-medicate with benzodiazepines. Selective GABA agents with novel mechanisms of action have anxiolytic, anticonvulsant, and reward inhibition profiles that have potential in treating substance use and withdrawal and enhancing relapse prevention with less liability than benzodiazepines. The GABA(B) receptor agonist baclofen has promise in relapse prevention in a number of substance dependence disorders. The GABA(A) and GABA(B) pump reuptake inhibitor tiagabine has potential for managing alcohol and sedative-hypnotic withdrawal and also possibly a role in relapse prevention. SN - 0160-6689 UR - https://www.unboundmedicine.com/medline/citation/12662132/GABA_systems_benzodiazepines_and_substance_dependence_ L2 - http://www.psychiatrist.com/jcp/article/pages/2003/v64s03/v64s0306.aspx DB - PRIME DP - Unbound Medicine ER -