Ethanol-conditioned place preference is reduced in dopamine D2 receptor-deficient mice

Pharmacological blockade studies have supported a role of the dopamine system in ethanol reward for many years, but receptor subtype specificity has been difficult to establish. Recently, genetically engineered mice lacking functional dopamine D2 receptors have been shown to drink less ethanol in a...

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Detalles Bibliográficos
Autores: Cunningham, Christopher L., Howard, MacKenzie A., Gill, Sylvia J., Rubinstein, Marcelo, Low, Malcolm J., Grandy, David K.
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2000
País:Argentina
Institución:Consejo Nacional de Investigaciones Científicas y Técnicas
Repositorio:CONICET Digital (CONICET)
Idioma:inglés
OAI Identifier:oai:ri.conicet.gov.ar:11336/71726
Acceso en línea:http://hdl.handle.net/11336/71726
Access Level:acceso abierto
Palabra clave:C57bl/6&Times;Dba/2 F2 Hybrid Mice
Conditioned Place Preference
Dopamine D2 Receptor
Ethanol
Knockout Mice
Locomotor Activity
https://purl.org/becyt/ford/3.1
https://purl.org/becyt/ford/3
Descripción
Sumario:Pharmacological blockade studies have supported a role of the dopamine system in ethanol reward for many years, but receptor subtype specificity has been difficult to establish. Recently, genetically engineered mice lacking functional dopamine D2 receptors have been shown to drink less ethanol in a two-bottle choice task. To determine whether reduced ethanol intake reflects a reduction in ethanol reward, D2 receptor-deficient [knockout (KO)] mice were compared to heterozygous (HET) and wild-type (WT; C57BL/6 × DBA/2 F2 hybrid) mice in a place conditioning task. Under conditions that produced reliable place preference in both WT and HET mice, KO mice showed no evidence of place conditioning, suggesting that D2 receptor gene inactivation reduced ethanol reward or the ability to learn about ethanol reward. Consistent with previous findings, this mutation also produced a gene dose-related reduction in basal activity levels. Moreover, KO and HET mice showed enhancement of ethanol-stimulated activity relative to WT mice. However, differences in basal and ethanol-stimulated activity did not explain the differences in place conditioning. Overall, this study strongly supports the conclusion that dopamine D2 receptors normally influence ethanol reward in mice.