Ascending orexinergic pathways and alcohol-seeking

Orexin (hypocretin) containing neurons reside in discrete regions of the lateral hypothalamus from where they innervate the entire neuroaxis. Via actions upon orexin receptors (OX1 and OX2), the orexin peptides (orexin A and orexin B) are thought to play a role in ethanol consumption and seeking. While a role for OX1 receptors in these behaviours is established, the case for OX2 receptors is less clear at present, although recent data certainly support an involvement of OX2 receptors in ethanol consumption. In terms of circuitry, orexin receptors the ventral tegmental area appear to contribute to ethanol consumption. Other loci remain to be characterised, and we suggest prefrontal cortical orexin receptors deserve attention in this respect.

► Orexin-1 receptors are involved in ethanol reinforcement and multiple forms of ethanol-seeking behaviour. ► Orexin-2 receptors are involved in ethanol reinforcement. ► A role for orexin-2 receptors in ethanol-seeking is yet to be unequivocally determined. ► Possible sites of action include the ventral tegmental area and nucleus accumbens and should extend to include prefrontal regions.