Substance P in the anterior thalamic paraventricular nucleus: promotion of ethanol drinking in response to orexin from the hypothalamus.

The paraventricular nucleus of the thalamus (PVT) appears to participate in drug addiction. Recent evidence in rats shows that ethanol drinking is increased by orexin/hypocretin (OX) afferents from the hypothalamus, acting specifically in the anterior (aPVT) rather than posterior (pPVT) PVT subregion. The present study sought to identify neuropeptides transcribed within the PVT, which themselves might contribute to ethanol drinking and possibly mediate the actions of OX. We discovered that substance P (SP) in the aPVT can stimulate intermittent-access ethanol drinking, similar to OX, and that SP receptor [neurokinin 1 receptor/tachykinin receptor 1 (NK1R)] antagonists in this subregion reduce ethanol drinking. As with OX, this effect is site specific, with SP in the pPVT or dorsal third ventricle having no effect on ethanol drinking, and it is behaviorally specific, with SP in the aPVT reducing the drinking of sucrose and stimulating it in the pPVT. A close relationship between SP and OX was demonstrated by a stimulatory effect of local OX injection on SP mRNA and peptide levels, specifically in the aPVT but not pPVT, and a stimulatory effect of OX on SP expression in isolated thalamic neurons, reflecting postsynaptic actions. A functional relationship between OX and SP in the aPVT is suggested by our additional finding that ethanol drinking induced by OX is blocked by a local NK1R antagonist administered at a sub-threshold dose. These results, suggesting that SP in the aPVT mediates the stimulatory effect of OX on ethanol drinking, identify a new role for SP in the control of this behavior.

Short- and long-access palatable food self-administration results in different phenotypes of binge-type eating.

Binge eating disorder (BED), the most common eating disorder in the United States, is characterized by binge-type eating and is associated with higher body mass index and greater motivation for food. This disorder tends to first appear in late adolescence or young adulthood and is more common in women than men. While some animal models of BED have recapitulated both the overeating and the excessive body weight / fat of BED, very few have examined the motivational aspects of this disorder or utilized young females as subjects. In the present study, female Long-Evans rats, starting in late adolescence, were trained in operant chambers to self-administer the highly palatable Milk Chocolate Ensure Plus®, in 30-minute ("short access") or 6-hour ("long access") sessions, 5 days per week, over 6.5 weeks. For comparison, other subjects were provided with Ensure ad libitum or maintained on chow and water only. Both short and long access to Ensure led rats to develop binge-type eating, measured as greater 30-minute caloric intake than rats with ad libitum or chow access and as increasing 30-minute intake across weeks. Compared to those with short access, rats with long access demonstrated moderately increased motivation for Ensure (measured by progressive ratio testing) and, compared to those with only chow access, they eventually showed significant hyperphagia on Ensure access days and hypophagia on non-access days. Rats with long access also showed greater body weight/fat than those maintained on chow. These findings suggest that, while both short and long operant access to Ensure causes young female rats to meet the definition of binge-type eating, they lead to different phenotypes of this behavior, with long access promoting the development of a greater number of features found in clinical BED. Ultimately, both models may be useful in future studies aimed at identifying the neurobiological basis of binge eating.