Homer2 regulates alcohol and stress cross-sensitization

Autor(es)

Quadir, Sema G. ^[1] ; Borges dos Santos, Jaqueline Rocha ^[2] ; Campbell, Rianne R. ^[1] ; Wroten, Melissa G. ^[1] ; Singh, Nimrita ^[1] ; Holloway, John J. ^[1] ; Bal, Sukhmani K. ^[1] ; Camarini, Rosana ^[2] ; Szumlinski, Karen K. ^[1]

Afiliação do(s) autor(es)

^[1] Univ Calif Santa Barbara, Neurosci Res Inst, Dept Psychol & Brain Sci, Santa Barbara, CA 93106 - USA

^[2] Univ Sao Paulo, Inst Biomed Sci, Dept Pharmacol, Sao Paulo - Brazil

• Tipo de documento: Artigo Científico
• Fonte: ADDICTION BIOLOGY; v. 21, n. 3, p. 613-633, MAY 2016.
• Citações Web of Science: 16

Resumo

An interaction exists between stress and alcohol in the etiology and chronicity of alcohol use disorders, yet a knowledge gap exists regarding the neurobiological underpinnings of this interaction. In this regard, we employed an 11-day unpredictable, chronic, mild stress (UCMS) procedure to examine for stress-alcohol cross-sensitization of motor activity as well as alcohol consumption/preference and intoxication. We also employed immunoblotting to relate the expression of glutamate receptor-related proteins within subregions of the nucleus accumbens (NAC) to the manifestation of behavioral cross-sensitization. UCMS mice exhibited a greater locomotor response to an acute injection of 2g/kg alcohol than unstressed controls and this cross-sensitization extended to alcohol intake (0-20 percent), as well as to the intoxicating and sedative properties of 3 and 5g/kg alcohol, respectively. Regardless of prior alcohol injection (2g/kg), UCMS mice exhibited elevated NAC shell levels of mGlu1, GluN2b and Homer2, as well as lower phospholipase C within this subregion. GluN2b levels were also lower within the NAC core of UCMS mice. The expression of stress-alcohol locomotor cross-sensitization was associated with lower mGlu1 within the NAC core and lower extracellular signal-regulated kinase activity within both NAC subregions. As Homer2 regulates alcohol sensitization, we assayed also for locomotor cross-sensitization in Homer2 wild-type (WT) and knock-out (KO) mice. WT mice exhibited a very robust cross-sensitization that was absent in KO animals. These results indicate that a history of mild stress renders an animal more sensitive to the psychomotor and rewarding properties of alcohol, which may depend on neuroplasticity within NAC glutamate transmission. (AU)

• Processo FAPESP: 12/10260-7 - Análise das vias de ativação do CREB em camungondos adolescentes e adultos tratados com cocaína.
• Beneficiário: Rosana Camarini
• Modalidade de apoio: Auxílio à Pesquisa - Regular