Implication of the myo-inositol pathway in behavioral alterations of infected threespine sticklebacks

Threespine stickleback (Gasterosteus aculeatus) infected with the tapeworm
Schistocephalus solidus display impairments in their anti-predator
responses. They also have increased expression of the gene encoding the
IMPase 1 enzyme in their brains, which is part of a key step in
myo-inositol synthesis. IMPase 1 and myo-inositol levels are the targets
of lithium treatment in patients with bipolar disorder. Although promising
candidates, we do not know if IMPase 1 and myo-inositol are directly
implicated in the changes in risky behaviors measured in
Schistocephalus-infected fish. Understanding the molecular mechanisms
directly or indirectly involved in these behavioral alterations is crucial
to understand the evolution of host-parasite interactions. Here, we
increased myo-inositol levels of uninfected fish and inhibited IMPase 1
activity in infected fish to test the prediction that it would decrease
and increase their anti-predator behaviour, respectively. We found that
uninfected fish with increased myo-inositol levels (by injecting exogenous
myo-inositol or by inducing endogenous production using an osmotic
challenge) did not decrease their anti-predator responses. However,
infected fish treated with lithium chloride had some of their
anti-predator behaviors restored, but not all. They spent less time
swimming close to the surface, swam a shorter distance, had a higher
latency to feed, and spent more time frozen after a predator attack. Our
results suggest that the target of lithium treatment is implicated in the
risky behaviors of infected fish and supports the idea that the
parasite-associated alteration in behavior has a multifactorial nature.