Neurocircuitry targets in ethanol reward and dependence.
Alcoholism is a complex behavioral disorder characterized by excessive consumption of ethanol, a narrowing of the behavioral repertoire toward excessive consumption, the development of tolerance and dependence, and impairment in social and occupational functioning. Animal models of the complete syndrome of alcoholism are difficult if not impossible to achieve, but validated animal models exist for many of the different components of the syndrome. Recent work has begun to define the neurocircuits responsible for the two major sources of reinforcement key to animal models of excessive ethanol intake: positive and negative reinforcement. Ethanol appears to interact with ethanol-sensitive elements within neuronal membranes that convey the specificity of neurochemical action. Ethanol reinforcement appears to be mediated by an activation of GABA-A receptors, release of opioid peptides, release of dopamine, inhibition of glutamate receptors, and interaction with serotonin systems. These neurocircuits may be altered by chronic ethanol administration as reflected by opposite effects during acute ethanol withdrawal and by the recruitment of other neurotransmitter systems such as the stress neuropeptide corticotropin-releasing factor. Future challenges will include a focus on understanding how these neuroadaptive changes convey vulnerability to relapse in animals with a history of ethanol dependence.
Koob
G F
GF
Department of Neuropharmacology, The Scripps Research Institute, La Jolla, California 92037, USA.
Roberts
A J
AJ
Schulteis
G
G
Parsons
L H
LH
Heyser
C J
CJ
Hyytiä
P
P
Merlo-Pich
E
E
Weiss
F
F
D000428:Alcohol Drinking / Q000009:adverse effects / Q000503:physiopathology*; D000430:Alcohol Withdrawal Delirium / Q000503:physiopathology; D000437:Alcoholism / Q000503:physiopathology*; D000679:Amygdala / Q000187:drug effects / Q000503:physiopathology; D000818:Animals; D001921:Brain / Q000187:drug effects / Q000503:physiopathology; D003346:Corticotropin-Releasing Hormone / Q000502:physiology; D004298:Dopamine / Q000502:physiology; D006801:Humans; D009042:Motivation; D009415:Nerve Net / Q000187:drug effects / Q000503:physiopathology*; D018377:Neurotransmitter Agents / Q000502:physiology*; D017981:Receptors, Neurotransmitter / Q000187:drug effects / Q000502:physiology
D018377:Neurotransmitter Agents; D017981:Receptors, Neurotransmitter; D003346:Corticotropin-Releasing Hormone; D004298:Dopamine