Decreased brain reward produced by ethanol withdrawal.
Abstinence from chronic administration of various drugs of abuse such as ethanol, opiates, and psychostimulants results in withdrawal syndromes largely unique to each drug class. However, one symptom that appears common to these withdrawal syndromes in humans is a negative affective/motivational state. Prior work in rodents has shown that elevations in intracranial self-stimulation (ICSS) reward thresholds provide a quantitative index that serves as a model for the negative affective state during withdrawal from psychostimulants and opiates. The current study sought to determine whether ICSS threshold elevations also accompany abstinence from chronic ethanol exposure sufficient to induce physical dependence. Rats prepared with stimulating electrodes in the lateral hypothalamus were trained in a discrete-trial current-intensity ICSS threshold procedure; subsequently they were subjected to chronic ethanol administration in ethanol vapor chambers (average blood alcohol level of 197 mg/dl). A time-dependent elevation in ICSS thresholds was observed following removal from the ethanol, but not the control, chambers. Thresholds were significantly elevated for 48 hr after cessation of ethanol exposure, with peak elevations observed at 6-8 hr. Blood alcohol levels were directly correlated with the magnitude of peak threshold elevation. Ratings of traditional overt signs of withdrawal showed a similar time course of expression and resolution. The results suggest that decreased function of reward systems (elevations in reward thresholds) is a common element of withdrawal from chronic administration of several diverse classes of abused drugs.
Schulteis
G
G
Department of Neuropharmacology, Scripps Research Institute, La Jolla, CA 92037, USA.
Markou
A
A
Cole
M
M
Koob
G F
GF
D000437:Alcoholism / Q000503:physiopathology* / Q000523:psychology; D000704:Analysis of Variance; D000818:Animals; D001921:Brain / Q000503:physiopathology*; D004558:Electric Stimulation; D000431:Ethanol / Q000097:blood; D007026:Hypothalamic Area, Lateral; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D012201:Reward; D012653:Self Stimulation; D013375:Substance Withdrawal Syndrome / Q000503:physiopathology* / Q000523:psychology; D013997:Time Factors
D000431:Ethanol