Animal models of alcoholism: Neurobiology of high alcohol-drinking behavior in rodents

William J. McBride, Ting Kai Li

Research output: Contribution to journalArticle

472 Citations (Scopus)

Abstract

This review discusses efforts to develop rodent models for the study of neurobiological mechanisms underlying chronic alcohol drinking, alcoholism, and abnormal alcohol-seeking behavior. Selective breeding has produced stable lines of rats that reliably exhibit high and (for comparison purposes) low voluntary alcohol consumption. In addition, animal models of chronic ethanol self-administration have been developed in rodents, who do not have a genetic predisposition for high alcohol-seeking behavior, to explore environmental influences in ethanol drinking and the effects of physical dependence on alcohol self-administration. The selectively bred high-preference animals reliably self-administer ethanol by free-choice drinking and operantly respond for oral ethanol in amounts that produce pharmacologically meaningful blood alcohol concentrations (50 to 200 mg% and higher). In addition, the alcohol-preferring rats will self-administer ethanol by intragastric infusion. With chronic free-choice drinking, the high alcohol-preferring rats develop tolerance to the high-dose effects of ethanol and show signs of physical dependence after the withdrawal of alcohol. Compared with nonpreferring animals, the alcohol-preferring rats are less sensitive to the sedative-hypnotic effects of ethanol and develop tolerance more quickly to high-dose ethanol. Nonselected common stock rats can be trained to chronically self-administer ethanol following its initial presentation in a palatable sucrose or saccharin solution, and the gradual replacement of the sucrose or saccharin with ethanol (the sucrose/saccharin-fade technique). Moreover, rats that are trained in this manner and then made dependent by ethanol-vapor inhalation or liquid diet increase their ethanol self-administration during the withdrawal period. Both the selectively bred rats and common-stock rats demonstrate 'relapse' and an alcohol deprivation effect following 2 or more weeks of abstinence. Systemic administration of agents that (1) increase synaptic levels of serotonin (5-HT) or dopamine (DA); (2) activate 5-HT(1A), 5-HT2, D2, D3, or GABA(A) receptors; or (3) block opioid and 5-HT3 receptors decrease ethanol intake in most animal models. Neurochemical, neuroanatomical, and neuropharmacological studies indicate innate differences exist between the high alcohol-consuming and low alcohol-consuming rodents in various CNS limbic structures. In addition, reduced mesolimbic DA and 5-HT function have been observed during alcohol withdrawal in common stock rats. Depending on the animal model under study, abnormalities in the mesolimbic dopamine pathway, and/or the serotonin, opioid, and GABA systems that regulate this pathway may underlie vulnerability to the abnormal alcohol-seeking behavior in the genetic animal models.

Original languageEnglish
Pages (from-to)339-369
Number of pages31
JournalCritical Reviews in Neurobiology
Volume12
Issue number4
StatePublished - 1998

Fingerprint

Drinking Behavior
Neurobiology
Alcohol Drinking
Alcoholism
Rodentia
Ethanol
Animal Models
Alcohols
Serotonin
Saccharin
Self Administration
Sucrose
Dopamine
Hypnotics and Sedatives
Opioid Analgesics
Drinking
Receptors, Serotonin, 5-HT3
Genetic Models
GABA-A Receptors
Genetic Predisposition to Disease

Keywords

  • Alcohol self-administration
  • Alcohol tolerance
  • Alcohol-reward pathway
  • Alcoholism
  • Animal model
  • Pharmacotherapy
  • Physical dependence
  • Rodents

ASJC Scopus subject areas

  • Clinical Neurology
  • Physiology
  • Neuroscience(all)

Cite this

Animal models of alcoholism : Neurobiology of high alcohol-drinking behavior in rodents. / McBride, William J.; Li, Ting Kai.

In: Critical Reviews in Neurobiology, Vol. 12, No. 4, 1998, p. 339-369.

Research output: Contribution to journalArticle

McBride, William J. ; Li, Ting Kai. / Animal models of alcoholism : Neurobiology of high alcohol-drinking behavior in rodents. In: Critical Reviews in Neurobiology. 1998 ; Vol. 12, No. 4. pp. 339-369.
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