Background
Social stress is a risk factor for affective disorders for certain vulnerable individuals.
Stress and depression are linked in part through regulation of the dorsal raphe (DR)-serotonin
(5-HT) system by the stress-related neuropeptide, corticotropin-releasing factor (CRF).
We used a rat social stress model that shows individual differences in coping strategies
to determine whether differences in CRF-5-HT interactions underlie individual differences
in the vulnerability to social stress.
Methods
Rats were exposed to the resident-intruder model of social stress for 5 days. In vivo
single-unit recordings assessed DR-5-HT neuronal responses to CRF and immunoelectron
microscopy assessed CRF1 and CRF2 cellular localization 24 hours after the last stress.
Results
Rats responded to social stress passively, assuming defeat with short latencies (48%),
or actively, with proactive behaviors and longer defeat latencies (LL, 52%). Whereas
CRF (30 ng, intra-DR) inhibited 5-HT neuronal activity of control and SL rats, it
activated 5-HT neurons of LL rats, an effect that was CRF2-mediated. Consistent with this, social stress promoted CRF1 internalization together with CRF2 recruitment to the plasma membrane of DR neurons selectively in LL rats.
Conclusions
These data suggest that a proactive coping strategy toward social stress is associated
with a redistribution of CRF1 and CRF2 in DR-5-HT neurons that primes the system to be activated by subsequent stress. The
lack of this adaptation in passive coping rats may contribute to their depressive-like
phenotype. These studies provide a cellular mechanism for individual differences in
stress responses and consequences.
Key Words
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Article info
Publication history
Published online: March 01, 2013
Accepted:
January 24,
2013
Received in revised form:
January 23,
2013
Received:
December 11,
2012
Identification
Copyright
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