D1 dopamine receptor-mediated LTP at GABA synapses encodes motivation to self-administer cocaine in rats.
J Neurosci
; 33(29): 11960-71, 2013 Jul 17.
Article
em En
| MEDLINE
| ID: mdl-23864683
ABSTRACT
Enhanced motivation to take drugs is a central characteristic of addiction, yet the neural underpinning of this maladaptive behavior is still largely unknown. Here, we report a D1-like dopamine receptor (DRD1)-mediated long-term potentiation of GABAA-IPSCs (D1-LTPGABA) in the oval bed nucleus of the stria terminalis that was positively correlated with motivation to self-administer cocaine in rats. Likewise, in vivo intra-oval bed nucleus of the stria terminalis DRD1 pharmacological blockade reduced lever pressing for cocaine more effectively in rats showing enhanced motivation toward cocaine. D1-LTPGABA resulted from enhanced function and expression of G-protein-independent DRD1 coupled to c-Src tyrosine kinases and required local release of neurotensin. There was no D1-LTPGABA in rats that self-administered sucrose, in those with limited cocaine self-administration experience, or in those that received cocaine passively (yoked). Therefore, our study reveals a novel neurophysiological mechanism contributing to individual motivation to self-administer cocaine, a critical psychobiological element of compulsive drug use and addiction.
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Base de dados:
MEDLINE
Assunto principal:
Sinapses
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Receptores de Dopamina D1
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Cocaína
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Potenciação de Longa Duração
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Inibidores da Captação de Dopamina
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Ácido gama-Aminobutírico
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Motivação
Idioma:
En
Ano de publicação:
2013
Tipo de documento:
Article