Download Modified Project Summary/Abstract Section

Title: K08-Stress adaptations in endocannabinoid signaling in the amygdala
Source: National Institute of Mental Health
Role: Principal investigator
Dates: July 1, 2010-June 30, 2015
Total Direct Costs: $ 700,000
ABSTRACT:
Psychosocial stress is a major risk factor for the precipitation and exacerbation of mental
illness in susceptible individuals. Understanding the neuroadaptations induced by
chronic stress could afford new opportunities for therapeutic intervention for stressrelated psychiatric disorders.
The candidate has shown that levels of the
endocannabinoid 2-arachidonoylglycerol (2-AG) exhibit a progressive increase in
response to repeated stress exposure in limbic brain regions including the amygdala,
and that this increase contributes stress-response habituation. In aim 1 of this proposal
the candidate will determine the temporal dynamics of the 2-AG response to stress and
the molecular mechanisms subserving these effects. The candidate will test the
hypothesis that the stress hormone corticosterone is required for the adaptations in
endogenous cannabinoid signaling to occur in response to repeated stress exposure.
Although stress increases 2-AG in the amygdala, it is not known if this increase is
associated with enhanced endocannabinoid-mediated synaptic signaling. In aim 2 the
candidate will test the hypothesis that this stress-induced increase in 2-AG in the
amygdala is associated with enhanced capacity of amygdala neurons to participate in
endocannabinoid-mediated synaptic signaling. Finally, in aim 3, the candidate will test
the hypothesis that stress-induced increases in 2-AG levels contribute to the behavioral
dysregulation induced by chronic stress. Elucidating the stress-induced adaptations in
endocannabinoid signaling could provide novel molecular targets for drug development
for the treatment of affective disorders.