Recruitment of a Neuronal Ensemble in the Central Nucleus of the Amygdala Is Required for Alcohol Dependence.
Abstinence from alcohol is associated with the recruitment of neurons in the central nucleus of the amygdala (CeA) in nondependent rats that binge drink alcohol and in alcohol-dependent rats. However, whether the recruitment of this neuronal ensemble in the CeA is causally related to excessive alcohol drinking or if it represents a consequence of excessive drinking remains unknown. We tested the hypothesis that the recruitment of a neuronal ensemble in the CeA during abstinence is required for excessive alcohol drinking in nondependent rats that binge drink alcohol and in alcohol-dependent rats. We found that inactivation of the CeA neuronal ensemble during abstinence significantly decreased alcohol drinking in both groups. In nondependent rats, the decrease in alcohol intake was transient and returned to normal the day after the injection. In dependent rats, inactivation of the neuronal ensemble with Daun02 produced a long-term decrease in alcohol drinking. Moreover, we observed a significant reduction of somatic withdrawal signs in dependent animals that were injected with Daun02 in the CeA. These results indicate that the recruitment of a neuronal ensemble in the CeA during abstinence from alcohol is causally related to excessive alcohol drinking in alcohol-dependent rats, whereas a similar neuronal ensemble only partially contributed to alcohol-binge-like drinking in nondependent rats. These results identify a critical neurobiological mechanism that may be required for the transition to alcohol dependence, suggesting that focusing on the neuronal ensemble in the CeA may lead to a better understanding of the etiology of alcohol use disorders and improve medication development.



Alcohol dependence recruits neurons in the central nucleus of the amygdala (CeA). Here, we found that inactivation of a specific dependence-induced neuronal ensemble in the CeA reversed excessive alcohol drinking and somatic signs of alcohol dependence in rats. These results identify a critical neurobiological mechanism that is required for alcohol dependence, suggesting that targeting dependence neuronal ensembles may lead to a better understanding of the etiology of alcohol use disorders, with implications for diagnosis, prevention, and treatment.
Committee on the Neurobiology of Addictive Disorders, The Scripps Research Institute, La Jolla, California 92037, and.
Giordano
0000-0002-4782-7430
G
de Guglielmo
Committee on the Neurobiology of Addictive Disorders, The Scripps Research Institute, La Jolla, California 92037, and.
Elena
E
Crawford
Committee on the Neurobiology of Addictive Disorders, The Scripps Research Institute, La Jolla, California 92037, and.
Sarah
S
Kim
Committee on the Neurobiology of Addictive Disorders, The Scripps Research Institute, La Jolla, California 92037, and.
Leandro F
0000-0002-8829-8627
LF
Vendruscolo
National Institute on Drug Abuse, Intramural Research Program, National Institutes of Health, Baltimore, Maryland 21224.
Bruce T
0000-0001-5804-7061
BT
Hope
Committee on the Neurobiology of Addictive Disorders, The Scripps Research Institute, La Jolla, California 92037, and.
Molly
0000-0002-5443-1100
M
Brennan
Committee on the Neurobiology of Addictive Disorders, The Scripps Research Institute, La Jolla, California 92037, and.
Maury
M
Cole
Committee on the Neurobiology of Addictive Disorders, The Scripps Research Institute, La Jolla, California 92037, and.
George F
GF
Koob
Committee on the Neurobiology of Addictive Disorders, The Scripps Research Institute, La Jolla, California 92037, and ogeorge@scripps.edu.
Olivier
0000-0002-3700-5003
O
George
D000437:Alcoholism / Q000473:pathology*; D000818:Animals; D066274:Central Amygdaloid Nucleus / Q000166:cytology* / Q000187:drug effects; D002492:Central Nervous System Depressants / Q000494:pharmacology; D003216:Conditioning, Operant / Q000187:drug effects; D003630:Daunorubicin / Q000031:analogs & derivatives / Q000494:pharmacology; D004195:Disease Models, Animal; D000431:Ethanol / Q000008:administration & dosage; D008297:Male; D009415:Nerve Net / Q000187:drug effects / Q000502:physiology*; D009474:Neurons / Q000502:physiology* / Q000528:radiation effects; D016761:Oncogene Proteins v-fos / Q000235:genetics / Q000378:metabolism; D051381:Rats; D055647:Rats, Transgenic; D012055:Reinforcement Schedule; D012646:Self Administration; D018709:Statistics, Nonparametric; D013997:Time Factors
D002492:Central Nervous System Depressants; C576267:N-(4''-(galactopyranosyl)-3''-nitrobenzyloxycarbonyl)daunomycin; D016761:Oncogene Proteins v-fos; D000431:Ethanol; D003630:Daunorubicin
CeA; Daun02; addiction; alcohol; dependence; neuronal ensembles