Knockdown of ventral tegmental area mu-opioid receptors in rats prevents effects of social defeat stress: implications for amphetamine cross-sensitization, social avoidance, weight regulation and expression of brain-derived neurotrophic factor.
Knockdown of ventral tegmental area mu-opioid receptors in rats prevents effects of social defeat stress: implications for amphetamine cross-sensitization, social avoidance, weight regulation and expression of brain-derived neurotrophic factor.
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DOI：
10.1016/j.neuropharm.2014.10.010
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发表时间：
2015-02
影响因子：
4.7
通讯作者：
Nikulina EM
中科院分区：
文献类型：
--
作者：
Johnston CE;Herschel DJ;Lasek AW;Hammer RP Jr;Nikulina EM
Social defeat stress causes social avoidance and long-lasting cross-sensitization to psychostimulants, both of which are associated with increased brain-derived neurotrophic factor (BDNF) expression in the ventral tegmental area (VTA). Moreover, social stress upregulates VTA mu-opioid receptor (MOR) mRNA. In the VTA, MOR activation inhibits GABA neurons to disinhibit VTA dopamine neurons, thus providing a role for VTA MORs in the regulation of psychostimulant sensitization. The present study determined the effect of lentivirus-mediated MOR knockdown in the VTA on the consequences of intermittent social defeat stress, a salient and profound stressor in humans and rodents. Social stress exposure induced social avoidance and attenuated weight gain in animals with non-manipulated VTA MORs, but both these effects were prevented by VTA MOR knockdown. Rats with non-manipulated VTA MOR expression exhibited cross-sensitization to amphetamine challenge (1.0 mg/kg, i.p.), evidenced by a significant augmentation of locomotion. By contrast, knockdown of VTA MORs prevented stress-induced cross-sensitization without blunting the locomotor-activating effects of amphetamine. At the time point corresponding to amphetamine challenge, immunohistochemical analysis was performed to examine the effect of stress on VTA BDNF expression. Prior stress exposure increased VTA BDNF expression in rats with non-manipulated VTA MOR expression, while VTA MOR knockdown prevented stress-induced expression of VTA BDNF. Taken together, these results suggest that upregulation of VTA MOR is necessary for the behavioral and biochemical changes induced by social defeat stress. Elucidating VTA MOR regulation of stress effects on the mesolimbic system may provide new therapeutic targets for treating stress-induced vulnerability to substance abuse.
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影响因子：
5.7
作者：
Lutz PE;Kieffer BL
通讯作者：
Kieffer BL
影响因子：
15.9
作者：
Lutz PE;Kieffer BL
通讯作者：
Kieffer BL
DOI：
10.1126/science.1222265
发表时间：
2012-10-05
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Koo JW;Mazei-Robison MS;Chaudhury D;Juarez B;LaPlant Q;Ferguson D;Feng J;Sun H;Scobie KN;Damez-Werno D;Crumiller M;Ohnishi YN;Ohnishi YH;Mouzon E;Dietz DM;Lobo MK;Neve RL;Russo SJ;Han MH;Nestler EJ
通讯作者：
Nestler EJ
影响因子：
4.7
作者：
Bergevin, A;Girardot, D;Trudeau, LE
通讯作者：
Trudeau, LE
影响因子：
1.7
作者：
Han, Wenhua;Hata, Harumi;Ikeda, Kazutaka
通讯作者：
Ikeda, Kazutaka