Habitual behaviour associated with exposure to high-calorie diet is prevented by an orexin-receptor-1 antagonist

Habitual actions, which are associated with addictive behaviours, contribute to the loss of control of food seeking seen following exposure to calorie-dense foods in rats. Antagonism of orexin-receptor-1 (ORX-R1) has been shown to reduce a range of stimulus-driven feeding behaviours, but have yet to be implicated in the regulation of habitual actions. In the current study, male Long-Evans rats were given 'binge-like' access to high-calorie diet (HCD) or standard chow diet, and were subsequently trained to press a lever for food outcome. When lever responses were tested following outcome devaluation, chow-fed rats displayed goal-directed actions, whereas HCD-exposed rats displayed habitual actions. In study 1, it was shown that systemic administration of the ORX-R1 antagonist, SB-334867, prior to test restored goal-directed behaviour in HCD-exposed rats. In study 2, intra-nigral administration of SB-334867 similarly restored goal-directed behaviour, thereby implicating the substantia nigra as an important site for this effect. This study demonstrates that targeting ORX-R1 reduces habitual food seeking in male rats which may be important for understanding and treating compulsive feeding, obesity and binge eating disorder. This study also implicates the lateral hypothalamus, where ORX is produced, in mediating the expression of habits for the first time, and thus extends on the neurocircuits known to regulate habitual actions. Further investigation is required to determine whether the same effects are also seen in female rats, given that there are recognised sexual dimorphisms in feeding behaviour and a higher incidence of disordered eating in female than male populations.