Hypocretin is mainly expressed in the lateral hypothalamus. Unexpectedly, the mRNA for hypocretin was detected in the DRN and was 3 fold higher in the binge-drinking rats. The hypocretin mRNA may be in those axons that project from the hypothalamus to innervate the DRN (Xu et al., 2013). Although there is no difference in hypocretin mRNA levels between naïve iP and iNP animals, alcohol drinking increased the hypocretin mRNA levels in iP rats (Lawrence et al., 2006). A hypocretin antagonist (SB-334867) caused a significant decrease in response to ethanol in a cue induced reinstatement experiment (Lawrence et al., 2006). The DRN provides negative feedback via serotonergic projections to the lateral hypothalamus (Xu et al., 2013), so decreased serotonin signaling from the DRN could be expected to lead to decreased inhibition of hypocretin signaling. Both hypocretin receptors (Hcrtr1 and Hcrtr2) were decreased about 2 fold, which could intensify this effect.
