Abstract # 1747 Activation of indoleamine 2,3 dioxygenase does not mediate inflammation-induced reductions in incentive motivation

Abstract

While inflammation is implicated in the development of depression, the neurobiological mechanisms remain elusive. One of the reasons for this is the complexity of depression. To move forward we have decided to deconstruct depression into basic neurobiological units and focus on incentive motivation and anhedonia. Using an operant conditioning task in which mice have the choice between a high effort/high reward and a low effort/low reward mode of response we demonstrated inflammation affects willingness to exert an effort for the reward but does not reduce the sensitivity to the reward. To assess the importance of activation of indoleamine 2,3 dioxygenase (IDO1) in these effects, we compared IDO1-deficient to wild type mice. In accordance with our previous results (Vichaya et al, Neuropsychopharmacology 2014) wild type mice responded to lipopolysaccharide (LPS, 0.33 mg/kg intraperitoneal 24 h before) by a reduction in total responses and an increase in percent chocolate pellets earned. The same response to LPS was observed in IDO1 KO mice. To further assess motivation, food-deprived mice were submitted to a restricted schedule of food delivery that resulted in an increase in locomotor activity just before the expected delivery of food. This food-related anticipatory activity was decreased in the same manner by LPS in wild type and IDO1 KO mice. These findings indicate that inflammation-induced deficits in incentive motivation are not mediated by IDO1 activation.