RT Journal Article
ID 6a6fd02928abb6af
A1 McBride, William J.
A1 Li, Ting-Kai
T1 Animal Models of Alcoholism: Neurobiology of High Alcohol-Drinking Behavior in Rodents
JF Critical Reviews™ in Neurobiology
JO CRN
YR 1998
FD 1998-12-01
VO 12
IS 4
SP 339
OP 369
K1 animal model
K1 rodents
K1 alcoholism
K1 alcohol-reward pathway
K1 alcohol tolerance
K1 physical dependence
K1 alcohol self-administration
K1 pharmacotherapy
AB 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-HT1A, 5-HT2, D2, D3, or GABAA 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 GAB A systems that regulate this pathway may underlie vulnerability to the abnormal alcohol-seeking behavior in the genetic animal models.
PB Begell House
LK https://www.dl.begellhouse.com/journals/7b004699754c9fe6,3458781e2c1a2a0a,6a6fd02928abb6af.html