Alcohol and the Brain: Neuronal Molecular Targets, Synapses, and Circuits.
paper
Cited
Public
- Authors
- Abrahao, Karina P; Salinas, Armando G; Lovinger, David M
- Year
- 2017
- Journal
- Neuron
- PMID
- 29268093
- DOI
- 10.1016/j.neuron.2017.10.032
- PMCID
- PMC6566861
Ethanol is one of the most commonly abused drugs. Although environmental and genetic factors contribute to the etiology of alcohol use disorders, it is ethanol's actions in the brain that explain (1) acute ethanol-related behavioral changes, such as stimulant followed by depressant effects, and (2) chronic changes in behavior, including escalated use, tolerance, compulsive seeking, and dependence. Our knowledge of ethanol use and abuse thus relies on understanding its effects on the brain. Scientists have employed both bottom-up and top-down approaches, building from molecular targets to behavioral analyses and vice versa, respectively. This review highlights current progress in the field, focusing on recent and emerging molecular, cellular, and circuit effects of the drug that impact ethanol-related behaviors. The focus of the field is now on pinpointing which molecular effects in specific neurons within a brain region contribute to behavioral changes across the course of acute and chronic ethanol exposure.
Neurotransmitter/Modulator Systems and Molecular Targets of EthanolThe symbols and definitions shown here are used in Figures 2 and 3.
Acute Effects of Ethanol on the Hippocampus, Striatum, Cerebellum, Amygdala, and MidbrainBLA, basolateral amygdala; CeA, central amygdala; DLS, dorsolateral striatum; DMS, dorsomedial striatum; FSI, fast-spiking interneuron; iLTD, Inhibitory long-term depression; LTP, long-term potentiation; LTD, long-term depression; MSN, medium spiny neuron; SN/VTA, substantia nigra/ventral tegmental area. See text and Figure S1 for references related to each letter and highlighted effect.
Chronic Effects of Ethanol on the Frontal Cortex, Striatum, Hippocampus, Amygdala, and MidbrainBLA, basolateral amygdala; CeA, central amygdala; core, nucleus accumbens core; DLS, dorsolateral striatum; DMS, dorsomedial striatum; iLTP, inhibitory long-term potentiation; LTP, long-term potentiation; LTD, long-term depression; shell, nucleus accumbens shell; SN/VTA, substantia nigra/ventral tegmental area. See text and Figure S2 for explanation and references related to each letter and highlighted effect.
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| Name | Type |
|---|---|
| 5HT3 receptor local | drug |
| acute ethanol-induced increase in dopamine neuron firing local | phenotype |
| acute withdrawal | phenotype |
| addiction | phenotype |
| adenylyl cyclase | drug |
| ADH | gene |
| alcohol abuse | phenotype |
| alcohol intoxication | phenotype |
| alcohol-related behaviors | phenotype |
| Alcohol seeking | phenotype |
| alcohol self-administration | phenotype |
| alcohol sensitivity | phenotype |
| alcohol tolerance | phenotype |
| Alcohol Use Disorder | phenotype |
| AMPA-mediated transmission local | phenotype |
| amygdala | anatomy |
| animal models | cohort |
| Apical dendrites local | anatomy |
| Appetitive behavior local | phenotype |
| Associative circuit local | anatomy |
| associative striatum local | anatomy |
| Associative striatum local | anatomy |
| aversion | phenotype |
| Aversive stimuli processing local | phenotype |
| barbiturates | drug |
| Barium-sensitive potassium local | drug |
| Basal dendrites local | anatomy |
| basolateral amygdala | anatomy |
| behavioral consequences | phenotype |
| Behavioral tolerance local | phenotype |
| binge drinking | phenotype |
| BK channel | gene |
| BNST | anatomy |
| BNST-VTA projection neurons local | anatomy |
| brain | anatomy |
| brain circuits | anatomy |
| C57BL/6J | cohort |
| C57 mice local | cohort |
| Caenorhabditis elegans | cohort |
| central amygdala | anatomy |
| cerebellar granule cells | anatomy |
| cerebellum | anatomy |
| chemogenetics local | drug |
| cholinergic | drug |
| chronic ethanol exposure | phenotype |
| cognition | phenotype |
| conditioned place preference | phenotype |
| Consummatory behavior local | phenotype |
| context-induced relapse local | phenotype |
| cortex | anatomy |
| Corticostriatal synapse | anatomy |
| corticotropin-releasing factor | drug |
| CRF | drug |
| CRF1R | drug |
| CRHR1 | gene |
| cysβloop LGICs local | drug |
| DBA local | cohort |
| DBA mice local | cohort |
| depolarization | phenotype |
| depressive behavior | phenotype |
| dopamine | drug |
| dopamine release | drug |
| dopaminergic neurons | anatomy |
| dorsal striatum | anatomy |
| DRD2 | gene |
| Drosophila melanogaster | cohort |
| drug dependence | phenotype |
| Emotional salience local | phenotype |
| Endocannabinoid-mediated disinhibition local | phenotype |
| enhanced ethanol intake local | phenotype |
| enkephalin | drug |
| Ethanol-associated behaviors local | phenotype |
| ethanol consumption | phenotype |
| Ethanol-induced analgesia local | phenotype |
| ethanol insensitivity local | phenotype |
| Ethanol locomotor sensitization local | phenotype |
| ethanol-related behaviors | phenotype |
| Ethanol-sensitization-resistant mice local | cohort |
| Ethanol-sensitization-susceptible mice local | cohort |
| excessive alcohol consumption | phenotype |
| excessive ethanol intake local | phenotype |
| excessive ethanol seeking local | phenotype |
| firing | phenotype |
| frontal cortex | anatomy |
| GABA | phenotype |
| GABAA receptor | drug |
| GABA-mimetic drugs local | drug |
| Gabrd | gene |
| Gamma-aminobutyric acid | drug |
| Gi/o-coupled GPCRs local | drug |
| GIRK3 subunit knockout mice local | cohort |
| Globus pallidus external segment local | anatomy |
| GLRA2 local | gene |
| Glra3 | gene |
| glutamate | drug |
| Glutamate receptors local | phenotype |
| Glutamate reuptake inhibition local | drug |
| glycine receptor | drug |
| GlyR | drug |
| GlyR local | gene |
| Goal-directed actions local | phenotype |
| GRIN2B | gene |
| GRM2 | gene |
| GRM5 | gene |
| growth factors | drug |
| G. violaceus LGIC local | drug |
| Habitual actions local | phenotype |
| HCN channel local | drug |
| hippocampal CA1 region | anatomy |
| hippocampus | anatomy |
| humans | cohort |
| hyperglutamatergic state | phenotype |
| hyperpolarization | phenotype |
| Ih density local | phenotype |
| impulsivity | phenotype |
| Increased firing rate local | phenotype |
| increased NAc dopamine levels local | phenotype |
| infralimbic cortex | anatomy |
| Inhibitory effect on glutamate release local | phenotype |
| insula | anatomy |
| intracellular signaling proteins local | drug |
| ion channel subunits local | drug |
| ionotropic glutamate receptor | drug |
| Kcnj6 | gene |
| Kcnj9 | gene |
| Kcnma1 | gene |
| Kcnmb4 | gene |
| large-scale brain circuitry local | anatomy |
| learning and memory | phenotype |
| locomotion | phenotype |
| locomotor depression | phenotype |
| locomotor sensitization | phenotype |
| long-term depression | phenotype |
| long-term potentiation | phenotype |
| LTD | phenotype |
| LTP | phenotype |
| medial prefrontal cortex | anatomy |
| Membrane fluidity local | phenotype |
| membrane lipids | drug |
| mesolimbic dopamine system | drug |
| mGluR2 knockout mouse local | cohort |
| mGluR5 | drug |
| mice | cohort |
| midbrain | anatomy |
| Missense mutation in GIRK channel local | variant |
| Mouse model of binge drinking local | cohort |
| M-type currents local | drug |
| naltrexone | drug |
| negative affect | phenotype |
| neuronal excitability | phenotype |
| neuronal function | phenotype |
| neuronal projections local | anatomy |
| neurophysiological effects local | phenotype |
| neurosteroids | drug |
| nicotinic acetylcholine receptor | drug |
| nitric oxide synthase | drug |
| NMDA-mediated transmission local | phenotype |
| NMDAR | drug |
| NMDAR-dependent LTD local | phenotype |
| NMDA receptor | drug |
| N-methyl-D-aspartate receptor local | gene |
| NR2C subunit local | drug |
| nucleus accumbens | anatomy |
| nucleus accumbens core | anatomy |
| nucleus accumbens shell | anatomy |
| opiates | drug |
| opioid | drug |
| opioid receptor | drug |
| Oprd1 | cohort |
| OPRK1 | cohort |
| optogenetics local | drug |
| PKC epsilon local | drug |
| P rats | cohort |
| prefrontal cortex | anatomy |
| Presynaptic potentiation of glutamate release local | phenotype |
| protein kinase A | drug |
| Protein kinase C | drug |
| proteins involved in epigenetic regulation of gene expression local | drug |
| Reinforcing behavior local | phenotype |
| relapse | phenotype |
| reward | phenotype |
| rodents | cohort |
| sensitization | phenotype |
| sensorimotor circuit | anatomy |
| Serotoninergic local | drug |
| SK2 channel local | gene |
| SK channel local | gene |
| SK channel activator local | drug |
| SK channel inhibition local | phenotype |
| SLC6A9 | gene |
| stress | phenotype |
| striatal medium spiny neurons local | anatomy |
| striatum | anatomy |
| subiculum | anatomy |
| synaptic plasticity | phenotype |
| taurine | drug |
| thalamus | anatomy |
| TM3 domain mutation local | variant |
| transcription factors | drug |
| ventral medial prefrontal cortex | anatomy |
| ventral subiculum | anatomy |
| ventral tegmental area | anatomy |
| VTA | anatomy |
| VTA dopamine neurons local | phenotype |
| water | drug |
| withdrawal anxiety-like behavior local | phenotype |
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