Ethanol interaction with α3ß4 nicotinic acetylcholine receptors in neurons of the laterodorsal tegmentum.
Alcohol Clin Exp Res
; 45(12): 2495-2505, 2021 12.
Article
em En
| MEDLINE
| ID: mdl-34625982
ABSTRACT
BACKGROUND:
Nicotinic acetylcholine receptors (nAChRs) play a key role in the rewarding effects of ethanol (EtOH), and while several nAChR subtypes have been implicated, attention has recently shifted to a role for the α3ß4 nAChR. The laterodorsal tegmental nucleus (LDTg), a brainstem cholinergic nucleus that sends excitatory projections to the ventral tegmental area, is an Integral part of the brain reward pathway. Here we investigate a potential role for LDTg α3ß4 nAChRs in EtOH self-administration and reward.METHODS:
Sprague-Dawley rats were given ad libitum access to a 20% EtOH solution, as part of a two-bottle choice paradigm. Approximately 1 week after removal of EtOH access, we measured LDTg α3ß4 nAChR current responses to focal application of acetylcholine (ACh), using whole-cell patch clamp electrophysiology recordings in acute brain slices. In addition, we used whole-cell electrophysiology to assess the acute effects of EtOH on the sensitivity of LDTg α3ß4 nAChRs.RESULTS:
Focal application of ACh onto LDTg neurons resulted in large α3ß4 nAChR-mediated inward currents, the magnitude of which showed a positive correlation with levels of EtOH self-administration. In addition, using brain slices taken from EtOH-naïve rats, bath application of EtOH resulted in a moderate potentiation of LDTg α3ß4 nAChR sensitivity.CONCLUSIONS:
Using a rat model, increased α3ß4 nAChR function was associated with greater EtOH self-administration, with α3ß4 nAChR function also acutely potentiated by EtOH. Assuming that similar findings apply to humans, the α3ß4 nAChR could be a therapeutic target in the treatment of EtOH use disorder.Palavras-chave
Texto completo:
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Base de dados:
MEDLINE
Assunto principal:
Receptores Nicotínicos
/
Agonistas Nicotínicos
/
Neurônios
/
Nicotina
Tipo de estudo:
Prognostic_studies
Limite:
Animals
Idioma:
En
Ano de publicação:
2021
Tipo de documento:
Article