Leptin-deficient mice retain normal appetitive spatial learning yet exhibit marked increases in anxiety-related behaviours

Rationale The individual's emotional state influences food intake in both humans and rodents. Moreover, specific cognitive processes regulating the salient aspects of food reward are also critical for ingestive behaviour. However, the molecular mechanisms underlying such influence remain unclear. Genetic mouse models thus are important tools in dissecting the molecular and pathophysiological processes which cause complex human diseases. Leptin, encoded by the ob gene, plays an important part in the energy homeostasis and is critical for the development of obesity. Objectives In these studies, we assess the impact of leptin on behaviours relevant to anxiety and appetitive learning. Methods Anxiety-related behaviour was assessed in the light dark box and two tests of hyponeophagia. Spatial learning and behavioural flexibility by re-learning was assessed in an appetitive Y-maze task. Results Leptin-deficient (ob/ob) mice displayed higher levels of anxiety-related behaviour in both anxiety tests. In the appetitive Y-maze task, leptin deficiency caused no deficit in learning or re-learning and acute restrained stress had no influence on the learning process. Conclusions These results emphasise that whilst leptin has previously been shown to modulate aversively motivated learning we found no difference between leptin-deficient mice and their controls in an appetitive learning task. Moreover, both groups showed behavioural flexibility under stressful conditions. On the other hand, leptin deficiency resulted in marked alterations in behaviours relevant to anxiety.