Palatable food self-administration and reinstatement are not affected by dual orexin receptor antagonism

Publication date: Available online 27 June 2017Source: Progress in Neuro-Psychopharmacology and Biological PsychiatryAuthor(s): Shaun Yon-Seng Khoo, Kelly J. Clemens, Gavan P. McNallyAbstractThe orexins are widely regarded potential therapeutic targets for a range of disorders of appetitive motivation, including obesity. The motivational activator theory, the first coherent account of the orexin system's role in appetitive motivation, predicts that orexin release motivates appetitive behaviour when the reinforcer is highly salient, available under a high unit-cost or when reward seeking is cue-driven. The present study tested the effect of intracerebroventricular (i.c.v.) administration of the highly potent and commercially available dual orexin receptor antagonist, TCS 1102, on self-administration and reinstatement of palatable food seeking in hungry and sated rats. TCS 1102 was also tested on FR1, FR5, FR10 and PR schedules. Orexin neuron activation was measured by c-Fos/orexin-A immunohistochemistry after cue-induced reinstatement, an extinction test, or a home-cage control. No effect of i.c.v. TCS 1102 was observed on self-administration at any fixed or progressive ratio schedule of reinforcement or reinstatement in hungry or sated rats. Although there was robust recruitment of orexin neurons during behavioural testing conditions, there was no specific activation of these neurons during cue-induced reinstatement when compared to extinction testing conditions. These result...
Source: Progress in Neuro Psychopharmacology and Biological Psychiatry - Category: Psychiatry Source Type: research