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Presynaptic Ethanol Actions: Potential Roles in Ethanol Seeking.
1Laboratory for Integrative Neuroscience, Division of Intramural Clinical and Biological Research, National Institute on Alcohol Abuse and Alcoholism, Bethesda, MD, USA. lovindav@mail.nih.gov.
Handbook of Experimental Pharmacology
|December 6, 2017
Summary
Ethanol alters brain cell communication, particularly affecting GABAergic synapses. Chronic alcohol use leads to neuroadaptations in synaptic transmission, contributing to problematic drinking behaviors.
Area of Science:
- Neuroscience
- Pharmacology
- Molecular Biology
Background:
- Ethanol (alcohol) affects numerous molecular and cellular targets in the central nervous system (CNS).
- Chronic alcohol consumption leads to neuroadaptations that contribute to continued and problematic drinking.
- Presynaptic mechanisms of synaptic transmission, including protein function and excitation-secretion coupling, are key targets of ethanol's actions.
Purpose of the Study:
- To discuss the acute and chronic presynaptic effects of ethanol in the CNS.
- To explore the consequences of these effects on amygdala and corticostriatal circuits.
- To understand how presynaptic neuroadaptations contribute to behavioral changes at different stages of alcohol drinking.
Main Methods:
- Review of studies over the last 20-25 years on ethanol's effects on synaptic transmission.
- Analysis of alterations in presynaptic neurotransmitter receptors, particularly G protein-coupled receptors (GPCRs).
- Investigation of intracellular signaling pathways involving cyclic AMP and calcium.
Main Results:
- Acute ethanol exposure alters neurotransmitter secretion, with significant effects on gamma-aminobutyric acid (GABA) synapses.
- Ethanol-induced release of neuropeptides and small molecule neurotransmitters impacts GPCRs, affecting synaptic potentiation and inhibition.
- Prolonged ethanol exposure alters neurotransmitter release at GABAergic and glutamatergic synapses, with GPCR function changes implicated in neuroadaptations.
Conclusions:
- Presynaptic neuroadaptations to ethanol can involve compensation for acute effects or allostatic resetting of synaptic efficacy.
- These adaptations in CNS circuits are crucial for understanding excessive alcohol seeking and abuse.
- Further research is needed to elucidate the role of circuit adaptations in alcohol drinking behaviors.
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