Citation

Miczek KA, Nikulina EM, Takahashi A, Covington HE, Yap JJ, Boyson CO, Shimamoto A, de Almeida RMM. Behav. Genet. 2011; 41(6): 787-802.

Affiliation

Department of Psychology, Tufts University, 530 Boston Ave. (Bacon Hall), Medford, MA, 02155, USA, klaus.miczek@tufts.edu.

Copyright

(Copyright © 2011, Holtzbrinck Springer Nature Publishing Group)

DOI

10.1007/s10519-011-9462-5

PMID

21416141

Abstract

In this review, we examine how experiences in social confrontations alter gene expression in mesocorticolimbic cells. The focus is on the target of attack and threat due to the prominent role of social defeat stress in the study of coping mechanisms and victimization. The initial operational definition of the socially defeated mouse by Ginsburg and Allee (1942) enabled the characterization of key endocrine, cardiovascular, and metabolic events during the initial response to an aggressive opponent and during the ensuing adaptations. Brief episodes of social defeat stress induce an augmented response to stimulant challenge as reflected by increased locomotion and increased extracellular dopamine (DA) in the nucleus accumbens (NAC). Cells in the ventral tegmental area (VTA) that project to the NAC were more active as indicated by increased expression of c-fos and Fos-immunoreactivity and BDNF. Intermittent episodes of social defeat stress result in increased mRNA for MOR in brainstem and limbic structures. These behavioral and neurobiological indices of sensitization persist for several months after the stress experience. The episodically defeated rats also self-administered intravenous cocaine during continuous access for 24 h ("binge"). By contrast, continuous social stress, particularly in the form of social subordination stress, leads to reduced appetite, compromised endocrine activities, and cardiovascular and metabolic abnormalities, and prefer sweets less as index of anhedonia. Cocaine challenges in subordinate rats result in a blunted psychomotor stimulant response and a reduced DA release in NAC. Subordinate rats self-administer cocaine less during continuous access conditions. These contrasting patterns of social stress result from continuous vs. intermittent exposure to social stress, suggesting divergent neuroadaptations for increased vulnerability to cocaine self-administration vs. deteriorated reward mechanisms characteristic of depressive-like profiles.

Language: en