PNAS: Scientists have figured out how caffeine could prevent chronically stressed individuals from developing stress-related mood and memory disorders, such as depression. The international team of researchers looked at mice brains and found that caffeine physically blocks a stress-related chemical from connecting with its targets and triggering brain-changing events. Researchers report a potential molecular explanation for how chronic stress induces mood disorders and suggest a possible therapeutic approach for stress-induced disorders.
Repeated stress is a risk factor
for psychiatric disorders such as depression and memory loss. Incidence
of depression and risk of suicide have been inversely correlated with
caffeine consumption. However, the molecular basis for this effect is
not known. Rodrigo Cunha and colleagues tested whether adenosine
A2A receptors (A2AR) in the brain, which are known targets of caffeine,
control the negative effects of chronic unpredictable stress. Mice
subjected to stress showed significant behavioral changes consistent
with increased anxiety and reduced memory, compared with unstressed
mice. The behavioral changes were accompanied by reduced synaptic
plasticity and synaptic protein density, compared with unstressed mice,
but caffeine consumption prevented several of these changes. Stress also
enhanced A2AR levels in synapses, and blocking A2AR using drugs or
deleting the gene for A2AR had the same effect as caffeine consumption.
Notably, drugs that blocked A2AR could not only prevent but also reverse
the stress-induced behavioral and synaptic changes. The results
implicate A2AR as a potential link between chronic stress and mental
health deterioration, and suggest that A2AR blockers might help treat
stress-induced declines in mood and memory.