Remission and resurgence of anxiety-like behavior across protracted withdrawal stages in ethanol-dependent rats.
BACKGROUND
Alcohol dependence is a chronic disorder in which withdrawal symptoms often persist after detoxification. The purpose of the present experiment was to characterize susceptibility to stress and anxiogenic stimuli in rats over an extended time period following ethanol withdrawal.


METHODS
Male Wistar rats were made dependent via ethanol vapor exposure. The rats were then tested in the elevated plus-maze during acute ethanol withdrawal (ACW, approximately 8 hour), early "protracted" withdrawal (EPW, 2 weeks), or late "protracted" withdrawal (LPW, 6, 12 weeks) following brief restraint or no stress. Principal components analysis was used to identify constructs underlying plus-maze behavior.


RESULTS
Three factors characterized plus-maze performance: anxiety, locomotor activity, and risk assessment/decision making. Spontaneous anxiety-like behavior was increased during ACW, decreased to levels of ethanol-naïve controls during EPW, but markedly resurged during LPW. Withdrawal did not alter sensitivity to the anxiety-like effects of restraint stress. All ethanol-dependent rats showed locomotor hypoactivity that, in contrast to anxiety, remained stable throughout all withdrawal stages. Neither ethanol withdrawal nor restraint stress altered mean "risk assessment/decision making" scores, though ethanol withdrawal altered the emission of "risk assessment/decision making" behavior in relation to anxiety-like behavior and behavioral activation state.


CONCLUSIONS
The findings illustrate and model the spontaneous, severe, and long-lasting nature of behavioral abnormalities that accompany withdrawal from chronic, intermittent ethanol intoxication. The dynamic remission and resurgence in symptoms of negative affect (i.e., behavioral signs of anxiety) during "protracted" withdrawal may complicate recovery from alcoholism.
Zhao
Yu
Y
Molecular and Integrative Neurosciences Department, Committee on the Neurobiology of Addictive Disorders, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA.
Weiss
Friedbert
F
Zorrilla
Eric P
EP
D000437:Alcoholism / Q000503:physiopathology*; D000818:Animals; D001007:Anxiety / Q000139:chemically induced* / Q000503:physiopathology; D002492:Central Nervous System Depressants / Q000009:adverse effects; D003071:Cognition / Q000502:physiology; D004195:Disease Models, Animal; D000431:Ethanol / Q000009:adverse effects; D008124:Locomotion / Q000502:physiology; D008297:Male; D015999:Multivariate Analysis; D051381:Rats; D017208:Rats, Wistar; D012008:Recurrence; D012074:Remission Induction; D012149:Restraint, Physical / Q000502:physiology; D013375:Substance Withdrawal Syndrome / Q000150:complications / Q000503:physiopathology / Q000523:psychology*; D013997:Time Factors
D002492:Central Nervous System Depressants; D000431:Ethanol