Vesicular glutamate transporter 2-containing neurons of the centrally-projecting Edinger-Westphal nucleus regulate alcohol drinking and body temperature.

Zuniga, Alfredo; Smith, Monique L; Caruso, Maya; Ryabinin, Andrey E

Zuniga, Alfredo; Smith, Monique L; Caruso, Maya; Ryabinin, Andrey E.

Afiliación

Zuniga A; Department of Behavioral Neuroscience, Oregon Health & Science University, 3181 SW Sam Jackson Park Road, Portland, OR, 97239, USA. Electronic address: Zuniga.alf@gmail.com.
Smith ML; Department of Behavioral Neuroscience, Oregon Health & Science University, 3181 SW Sam Jackson Park Road, Portland, OR, 97239, USA.
Caruso M; Department of Behavioral Neuroscience, Oregon Health & Science University, 3181 SW Sam Jackson Park Road, Portland, OR, 97239, USA.
Ryabinin AE; Department of Behavioral Neuroscience, Oregon Health & Science University, 3181 SW Sam Jackson Park Road, Portland, OR, 97239, USA.

Neuropharmacology ; 200: 108795, 2021 12 01.

Article en En | MEDLINE | ID: mdl-34555367

RESUMEN

Previous studies in rodents have repeatedly demonstrated that the centrally-projecting Edinger-Westphal nucleus (EWcp) is highly sensitive to alcohol and is also involved in regulating alcohol intake and body temperature. Historically, the EWcp has been known as the main site of Urocortin 1 (Ucn1) expression, a corticotropin-releasing factor-related peptide, in the brain. However, the EWcp also contains other populations of neurons, including neurons that express the vesicular glutamate transporter 2 (Vglut2). Here we transduced the EWcp with adeno-associated viruses (AAVs) encoding Designer Receptors Exclusively Activated by Designer Drugs (DREADDs) to test the role of the EWcp in alcohol drinking and in the regulation of body temperature. Activation of the EWcp with excitatory DREADDs inhibited alcohol intake in a 2-bottle choice procedure in male C57BL/6J mice, whereas inhibition of the EWcp with DREADDs had no effect. Surprisingly, analysis of DREADD expression indicated Ucn1-containing neurons of the EWcp did not express DREADDs. In contrast, AAVs transduced non-Ucn1-containing EWcp neurons. Subsequent experiments showed that the inhibitory effect of EWcp activation on alcohol intake was also present in male Ucn1 KO mice, suggesting that a Ucn1-devoid population of EWcp regulates alcohol intake. A final set of chemogenetic experiments showed that activation of Vglut2-expressing EWcp neurons inhibited alcohol intake and induced hypothermia in male and female mice. These studies expand on previous literature by indicating that a glutamatergic, Ucn1-devoid subpopulation of the EWcp regulates alcohol consumption and body temperature.

Asunto(s)

Temperatura Corporal/efectos de los fármacos; Drogas de Diseño/farmacología; Núcleo de Edinger-Westphal/efectos de los fármacos; Etanol/farmacología; Proteína 2 de Transporte Vesicular de Glutamato/efectos de los fármacos; Consumo de Bebidas Alcohólicas/patología; Animales; Regulación de la Temperatura Corporal/efectos de los fármacos; Dependovirus; Masculino; Ratones; Ratones Endogámicos C57BL; Ratones Noqueados; Urocortinas/efectos de los fármacos

Palabras clave

Alcohol; Centrally-projecting edinger westphal; Designer receptors exclusively activated by designer drugs; Glutamate; Thermoregulation; Urocortin

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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Temperatura Corporal / Drogas de Diseño / Etanol / Proteína 2 de Transporte Vesicular de Glutamato / Núcleo de Edinger-Westphal Límite: Animals Idioma: En Revista: Neuropharmacology Año: 2021 Tipo del documento: Article Pais de publicación: Reino Unido

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