Escalated cocaine self-administration and seeking in mice after repeated intermittent social stress: a corticotropin releasing factor mechanism
Han, Xiao.
2017
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Abstract: Social stress has been linked to drug use disorders in humans. This
dissertation employs mouse models to examine how social defeat stress influences cocaine
self-administration and seeking. One of the hypotheses underlying stress effects on drug
use disorders is the interaction between stress neuropeptide corticotropin releasing factor
(CRF) and mesolimbic dopamine system. To assess ... read morethis hypothesis, I employed social defeat
stress in male mice, mimicking some salient features of social stress in humans. In Aim 1
and 2, I evaluated the effects of social stress on cocaine self-administration and focused
on the role of CRF and its type 1 receptors (CRF R1) in the ventral tegmental area (VTA, a
dopamine-rich brain region). In Aim 3 and 4, I established a stress-induced reinstatement
mouse model and further explored the potential stress effects on cocaine seeking behavior.
The results demonstrated that repeated intermittent social defeat stress, contributed to
the escalation of cocaine self-administration and seeking in male mice. Additionally, these
behavior changes were concurrent with increased tonic CRF within the VTA. Moreover,
pharmacological manipulations of CRF R1 in the VTA can block the social stress-escalated
cocaine self-administration and seeking. However, escalation of cocaine-seeking behaviors
was concurrent with decreased extracellular dopamine release in the nucleus accumbens shell
(NAcSh). Together, these findings establish fundamental roles of CRF and CRF R1 in the VTA
in mediating repeated social defeat stress escalated cocaine self-administration and
cocaine seeking in male mice. CRF-R1 may be a mechanism for balancing the dysregulation of
social stress and reward in drug use disorders.
Thesis (Ph.D.)--Tufts University, 2017.
Submitted to the Dept. of Psychology.
Advisor: Klaus Miczek.
Committee: Joseph DeBold, Lisa Shin, and Elena Chartoff.
Keyword: Psychobiology.read less - ID:
- sb397m80w
- Component ID:
- tufts:20667
- To Cite:
- TARC Citation Guide EndNote
