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H omer2 regulates alcohol and stress cross‐sensitization
Author(s) -
Quadir Sema G.,
Santos Jaqueline Rocha Borges dos,
Campbell Rianne R.,
Wroten Melissa G.,
Singh Nimrita,
Holloway John J.,
Bal Sukhmani K.,
Camarini Rosana,
Szumlinski Karen K.
Publication year - 2016
Publication title -
addiction biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.445
H-Index - 78
eISSN - 1369-1600
pISSN - 1355-6215
DOI - 10.1111/adb.12252
Subject(s) - sensitization , nucleus accumbens , alcohol , chemistry , endocrinology , medicine , pharmacology , psychology , receptor , biochemistry , neuroscience
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 2 g/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 5 g/kg alcohol, respectively. Regardless of prior alcohol injection (2 g/kg), UCMS mice exhibited elevated NAC shell levels of m G lu1α, G lu N 2b and H omer2, as well as lower phospholipase Cβ within this subregion. G lu N 2b levels were also lower within the NAC core of UCMS mice. The expression of stress–alcohol locomotor cross‐sensitization was associated with lower m G lu1α within the NAC core and lower extracellular signal‐regulated kinase activity within both NAC subregions. As H omer2 regulates alcohol sensitization, we assayed also for locomotor cross‐sensitization in H omer2 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.