GABA transporter currents activated by protein kinase A excite midbrain neurons during opioid withdrawal.
Neuron
; 45(3): 433-45, 2005 Feb 03.
Article
em En
| MEDLINE
| ID: mdl-15694329
ABSTRACT
Adaptations in neurons of the midbrain periaqueductal gray (PAG) induced by chronic morphine treatment mediate expression of many signs of opioid withdrawal. The abnormally elevated action potential rate of opioid-sensitive PAG neurons is a likely cellular mechanism for withdrawal expression. We report here that opioid withdrawal in vitro induced an opioid-sensitive cation current that was mediated by the GABA transporter-1 (GAT-1) and required activation of protein kinase A (PKA) for its expression. Inhibition of GAT-1 or PKA also prevented withdrawal-induced hyperexcitation of PAG neurons. Our findings indicate that GAT-1 currents can directly increase the action potential rates of neurons and that GAT-1 may be a target for therapy to alleviate opioid-withdrawal symptoms.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Proteínas de Membrana Transportadoras
/
Síndrome de Abstinência a Substâncias
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Substância Cinzenta Periaquedutal
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Proteínas Quinases Dependentes de AMP Cíclico
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Transtornos Relacionados ao Uso de Opioides
/
Neurônios
Tipo de estudo:
Prognostic_studies
Limite:
Animals
Idioma:
En
Revista:
Neuron
Ano de publicação:
2005
Tipo de documento:
Article