Macrophage inhibitory cytokine-1 (MIC-1), also known as growth differentiation 
factor 15 (GDF15), is a stress response cytokine. MIC-1/GDF15 is secreted into 
the cerebrospinal fluid and increased levels of MIC-1/GDF15 are associated with 
a variety of diseases including cognitive decline. Furthermore, Mic-1/Gdf15 
knockout mice (Mic-1 KO) weigh more, have increased adiposity, associated with 
increased spontaneous food intake, and exhibit reduced basal energy expenditure 
and physical activity. The current study was designed to comprehensively 
determine the role of MIC-1/GDF15 on behavioural domains of male and female 
knockout mice including locomotion, exploration, anxiety, cognition, social 
behaviours, and sensorimotor gating. Mic-1 KO mice exhibited a task-dependent 
increase in locomotion and exploration and reduced anxiety-related behaviours 
across tests. Spatial working memory and social behaviours were not affected by 
Mic-1/Gdf15 deficiency. Interestingly, knockout mice formed an increased 
association with the conditioned stimulus in fear conditioning testing and also 
displayed significantly improved prepulse inhibition. Overall sex effects were 
evident for social behaviours, fear conditioning, and sensorimotor gating. This 
is the first study defining the role of Mic-1/Gdf15 in a number of behavioural 
domains. Whether the observed impact is based on direct actions of Mic-1/Gdf15 
deficiency on the CNS or whether the behavioural effects are mediated by 
indirect actions on e.g. other neurotransmitter systems must be clarified in 
future studies.