The dual orexin/hypocretin receptor antagonist, almorexant, in the ventral tegmental area attenuates ethanol self-administration

Recent studies have implicated the hypocretin/orexinergic system in reward-seeking behavior. Almorexant, a dual orexin/hypocretin R1 and R2 receptor antagonist, has proven effective in preclinical studies in promoting sleep in animal models and was in Phase III clinical trials for sleep disorders. The present study combines behavioral assays with in vitro biochemical and electrophysiological techniques to elucidate the role of almorexant in ethanol and sucrose intake. Using an operant self-administration paradigm, we demonstrate that systemic administration of almorexant decreased operant selfadministration of both 20% ethanol and 5% sucrose. We further demonstrate that intraventral tegmental area (VTA) infusions, but not intra substantia nigra infusions, of almorexant reduced ethanol self-administration. Extracellular recordings performed in VTA neurons revealed that orexin-A increased firing and this enhancement of firing was blocked by almorexant. The results demonstrate that orexin/hypocretin receptors in distinct brain regions regulate ethanol and sucrose mediated behaviors.

Pars pro toto: Experimental exhibition design and curatorial paradigms

'Pars pro toto: Experimental Exhibition Design and Curatorial Paradigms' is situated within the ongoing debate over the conflation of art and curating, and the subsequent tension between artistic autonomy and curatorial intervention. This practice-led research project acclimates these polarities using a collaborative and discursive curatorial methodology in the creation of two exhibitions. Both exhibitions, one digital and one primarily physical, investigated how the temporary exhibition can operate as a site for provocation, how the suggested methodology facilitates the relationship between artist and curator within this paradigm, and outlines factors that assist in expanding the definition of the contemporary curatorial role.