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Review
. 2008;31(3):215-30.

Translational studies of alcoholism: bridging the gap

Natalie M Zahr  1 , Edith V Sullivan
Affiliations
Review

Translational studies of alcoholism: bridging the gap

Natalie M Zahr et al. Alcohol Res Health. 2008.

Abstract

Human studies are necessary to identify and classify the brain systems predisposing individuals to develop alcohol use disorders and those modified by alcohol, while animal models of alcoholism are essential for a mechanistic understanding of how chronic voluntary alcohol consumption becomes compulsive, how brain systems become damaged, and how damage resolves. Our current knowledge of the neuroscience of alcohol dependence has evolved from the interchange of information gathered from both human alcoholics and animal models of alcoholism. Together, studies in humans and animal models have provided support for the involvement of specific brain structures over the course of alcohol addiction, including the prefrontal cortex, basal ganglia, cerebellum, amygdala, hippocampus, and the hypothalamic-pituitary-adrenal axis.

Keywords: Alcohol dependence; alcohol and other drug effects and consequences; alcoholism; animal models; animal studies; brain; chronic alcohol exposure; environmental factors; genetic factors; human studies; neurobiology; translational studies.

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Figures

Figure 1
Figure 1
A) DSM–IV criteria for alcohol dependence. B) Criteria for an animal model of alcoholism.
Figure 2
Figure 2
Sagittal human brain with cortical regions delineated.
Figure 3
Figure 3
Simplified schematic of excitatory (other pyramidal [P] neurons) and inhibitory (GABAergic interneurons [G]) input to a pyramidal neuron in the prefrontal cortex (PFC).
Figure 4
Figure 4
Simplified schematic of frontocerebellar circuitry. NOTES: DM = dorsomedial nucleus of the thalamus; Dn = dentate nucleus.
Figure 5
Figure 5
Left panel) Extended reward and oversight system. Right panel) Cortical and subcortical regions in the “reward network” in which alcoholics have smaller volumes (covaried for age and total cerebral volume). Smaller volumes are circled. NOTE: Amyg = amygdala; CGa, CGp = cingulate (anterior, posterior); dlPFC = dorsolateral prefrontal cortex; FOC = orbitofrontal cortex; Hipp = hippocampus; Hypo = hypothalamus; INS = insula; MB = mammillary bodies; NAC = nucleus accmbens; PHa, PHp = parahippocampal gyrus (ant, post); SC = subcallosal cortex; SLEA = sublentic-ular extended amygdala; TP = temporal pole; VntDC = ventral diencephalon. SOURCE: Reprinted from Biological Psychiatry, Vol. 64, No. 3, Makris, N.; Oscar-Berman, M; Jaffin, S.K.; Hodge, S.M.; et al. Decreased volume of the brain reward system in alcoholism. Copyright 2008, with permission from Elsevier.
Figure 6
Figure 6
A) Human hypothalamic–pituitary–adrenal brain stress system. B) Human extrahypothalamic cortiocotropin–releasing factor (CRF) brain stress system. C) Rodent extrahypothalamic CRF brain stress system. SOURCE: A and B from Koob, G.F., and Le Moal, M. Drug Addiction, Dysregulation of Reward, and Allostasis. Neuropsychopharmacology 24:97–129, 2001.; C from Koob G.F., Alcoholism: Allostasis and Beyond. Alcoholism: Clinical and Experimental Research 27(2):232–243, 2003. NOTES: ACTH = adrenocorticotrophin; AMYG = amygdala; BNST = bed nucleus of the stria terminalis; CRF = corticotropin-releasing factor; HPC = hippocampus; NE = nore-pinephine; PFC, prefrontal cortex; PIT = pituitary gland; PVN = paraventricular nucleus.
Figure 7
Figure 7
Schematic diagram representing the brain systems modified by alcohol.
See this image and copyright information in PMC

References

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