MR blockade
Blocking the MR impairs certain forms of memory retrieval, including
verbal, autobiographic, and visuo-spatial memory (Otte et al. ,
2007; Rimmele et al. , 2013; Young et al. , 2016). This
highlights the role of MR specifically in hippocampal-based memory. In
contrast, MR blockade did not affect learning and immediate memory
retrieval or working memory (Otte et al. , 2007; Cornelisse, Joels
and Smeets, 2011; Young et al. , 2016). Non-hippocampal cognitive
processes, such as selective attention and psychomotor speed, were also
unaffected by spironolactone (Otte et al. , 2007; Cornelisse,
Joels and Smeets, 2011). Thus, intact hippocampal MR activation appears
important for optimal human memory regulation. However, MR blockade
increases cortisol concentrations, potentially shifting MR/GR balance
towards more GR activation, and so GR involvement must still be
considered in these effects.
Another line of research investigated the role of MR after psychosocial
stress. Interestingly, spironolactone treatment prevented stress-induced
cortisol effects on response inhibition, stimulus-response learning and
delay conditioning Vogel et al. , 2016, 2017), including cognitive
function beyond hippocampus-dependent processes. On a neuronal level,
stress is associated with a reduced activation of the hippocampus,
enhanced amygdala activation and amygdala-striatal connectivity, which
were found to depend on MR availability (Vogel et al. , 2016,
2017). These studies emphazise the importance of amygdalae MR, in line
with the observation that MR blockade was most effective for emotional
stimuli (Rimmele et al. , 2013).
In sum, MR blockade has mostly impairing effects on human cognition,
which fits closely to the animal data. Of note, the observed effects
reflect a one-time administration of a MR antagonist, while the effects
of chronic or repeated MR blockade are less well investigated.
Importantly, one study treated obese individuals with low-dose
spironolactone over 6 weeks and found improved rather than impaired
learning performance (Rotenstein et al. , 2015). This may be
relevant to situations like obesity, which is associated with increased
MR activity in peripheral tissues and possibly in central tissues as
well (Infante et al. , 2017).