The influence of orexins on ethanol-induced behavioral sensitization in male mice.

Recent evidence indicates the involvement of orexin in reward circuitry and drug addiction. In the present study we evaluated the role of orexin in ethanol-induced behavioral sensitization. In the first experiment, Swiss male mice received seven administrations of saline or ethanol (2.2g/kg, i.p., chronic), every other day. On the last day of treatment, half of saline-treated mice received a saline injection (saline) whereas the other half received 2.2g/kg of ethanol (i.p., acute). Behavioral sensitization was assessed by locomotor activity tests and after the last one, immunoreactivity for orexin and Fos (ORX+Fos-ir) was assessed in the lateral hypothalamic area. Chronic ethanol treatment produced behavioral sensitization and a trend for greater ORX+Fos-ir. In the second experiment, mice were treated as in Experiment 1 and type 1 orexin receptor antagonist, SB334867 (20mg/kg), was administered before the ethanol challenge successfully blocking the expression of sensitization in mice chronically treated with EtOH. These results indicate that orexin plays a role in ethanol-induced behavioral sensitization.