Central nervous system mechanisms in alcohol relapse

W. J. McBride, A. D. Le, A. Noronha

Research output: Contribution to journalArticle

60 Citations (Scopus)

Abstract

Background: Alcohol relapse is a major problem in the treatment of alcohol abuse and alcoholism. Understanding the long-term neuronal alterations that promote relapse of alcohol drinking is critical for the development of pharmacotherapies to treat alcoholism and alcohol abuse. The major objectives of this workshop were to present recent findings, by using rodent models, on behavioral and neurobiological factors that may underlie alcohol relapse and the results of clinical and pharmacological treatment strategies for preventing relapse. Methods: Prolonged ethanol drinking and repeated periods of alcohol deprivation were studied in nonselected rats and in rats selectively bred for high alcohol preference (P rat). The expression of a robust alcohol deprivation effect (ADE) was used as a model for alcohol relapse in rodents. Operant techniques were used to examine responding for ethanol after deprivation in both rats and C57BL/6J mice. Environmental cues and stress were used to assess their effects on reinstatement of alcohol responding. Microdialysis and [14C]-2-deoxyglucose techniques were used to examine neuronal alterations associated with alcohol relapse. Results: Prolonged free-choice ethanol drinking followed by deprivation produced an ADE in both stock and P rats. These rats demonstrated loss of control on reinstatement after chronic drinking and after prolonged deprivation. Acamprosate and naltrexone effectively reduced the ADE in stock rats. Stress reinstated operant responding for alcohol, and rats trained to associate a cue with ethanol presentation increased responding on the ethanol-associated lever in the absence of ethanol. After repeated deprivations, P rats shifted their preference toward drinking higher concentrations of ethanol, which increased the magnitude and duration of the ADE. Stock rats also shifted their preference toward solutions with higher ethanol concentrations and demonstrated a loss of control after prolonged ethanol drinking and deprivation. Long-lasting alterations in neuronal activity, serotonin-3 receptor function, and dopamine neurotransmission within the mesolimbic system were evident after chronic drinking that followed a prolonged deprivation period. Conclusions: The ADE is a useful model for studying alcohol relapse in both rats and mice. The potential validity of this model is supported by the findings that acamprosate and naltrexone are effective in preventing the ADE in rodents, and both compounds have gained recognition for their therapeutic effects in clinical populations. Genetics, stress, and environmental cues are all important factors that influence alcohol relapse. Long-term alterations in neuronal activity within the mesolimbic system, which possibly involve dopamine and serotonin, may underlie alcohol relapse.

Original languageEnglish
Pages (from-to)280-286
Number of pages7
JournalAlcoholism: Clinical and Experimental Research
Volume26
Issue number2
StatePublished - 2002

Fingerprint

Neurology
Central Nervous System
Alcohols
Recurrence
Rats
Ethanol
Drinking
Alcoholism
Cues
Rodentia
Naltrexone
Dopamine
Receptors, Serotonin, 5-HT3
Drug therapy
Microdialysis
Deoxyglucose
Therapeutic Uses
Inbred C57BL Mouse
Synaptic Transmission
Alcohol Drinking

Keywords

  • Alcohol Addiction
  • Alcohol Deprivation Effect
  • Alcohol Relapse
  • Animal Models

ASJC Scopus subject areas

  • Medicine (miscellaneous)
  • Toxicology

Cite this

McBride, W. J., Le, A. D., & Noronha, A. (2002). Central nervous system mechanisms in alcohol relapse. Alcoholism: Clinical and Experimental Research, 26(2), 280-286.

Central nervous system mechanisms in alcohol relapse. / McBride, W. J.; Le, A. D.; Noronha, A.

In: Alcoholism: Clinical and Experimental Research, Vol. 26, No. 2, 2002, p. 280-286.

Research output: Contribution to journalArticle

McBride, WJ, Le, AD & Noronha, A 2002, 'Central nervous system mechanisms in alcohol relapse', Alcoholism: Clinical and Experimental Research, vol. 26, no. 2, pp. 280-286.
McBride, W. J. ; Le, A. D. ; Noronha, A. / Central nervous system mechanisms in alcohol relapse. In: Alcoholism: Clinical and Experimental Research. 2002 ; Vol. 26, No. 2. pp. 280-286.
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