Article

Chronic Stress Triggers Social Aversion via Glucocorticoid Receptor in Dopaminoceptive Neurons

Molecular Genetics, Neurophysiology and Behavior Group, Centre National de la Recherche Scientifique (CNRS) Unité Mixte de Recherche (UMR) 7224, 75005 Paris, France.
Science (Impact Factor: 33.61). 01/2013; 339(6117):332-335. DOI: 10.1126/science.1226767
Source: PubMed

ABSTRACT

Repeated traumatic events induce long-lasting behavioral changes that are key to organism adaptation and that affect cognitive, emotional, and social behaviors. Rodents subjected to repeated instances of aggression develop enduring social aversion and increased anxiety. Such repeated aggressions trigger a stress response, resulting in glucocorticoid release and activation of the ascending dopamine (DA) system. We bred mice with selective inactivation of the gene encoding the glucocorticoid receptor (GR) along the DA pathway, and exposed them to repeated aggressions. GR in dopaminoceptive but not DA-releasing neurons specifically promoted social aversion as well as dopaminergic neurochemical and electrophysiological neuroadaptations. Anxiety and fear memories remained unaffected. Acute inhibition of the activity of DA-releasing neurons fully restored social interaction in socially defeated wild-type mice. Our data suggest a GR-dependent neuronal dichotomy for the regulation of emotional and social behaviors, and clearly implicate GR as a link between stress resiliency and dopaminergic tone.

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    • "The role of GR in dopamine circuitry was explored using floxed GR mice crossed with dopaminoceptive/dopaminergic-specific Cre mice (Ambroggi et al, 2009). GR in dopaminoceptive neurons projecting from the ventral tegmental area (VTA) of the brainstem to the nucleus accumbens (NAc), cortex, and dorsal striatum, is critical for the normal social aversion response to repeated aggression stress (Barik et al, 2013). Deletion of GR specifically in nucleus accumbens neurons (GR D1Cre mice) completely abrogates the development of social aversion, while mice with deletion of GR in dopaminergic neurons of the VTA (GR "
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    • "Likewise, the neural activities of AC might be regulated by serotonin, which can explain the suppressive effect of stress observed in this study. Moreover, other neuromodulators, such as dopamine and GABA etc., are also reported to be involved in the modulation of neural response under different behavioral states (McAlonan et al., 2006; Barik et al., 2013). Because AC neurons receive multiple modulations together, the net effect of stress on each neuron is dependent on the balance of excitatory and inhibitory modulation. "
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    • "But it is possible that the promotion of the production and release of glucocorticoid by stress stimulation is involved . As mentioned above, glucocorticoid receptor stimulation in the prefrontal cortex increases the release of stress-related neuromodulator dopamine [28] in the prefrontal cortex, through the positive-feedback system to midbrain dopamine neurons [35]. "

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