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.