## 3 Orexins and Food Intake in Experimental Animal Models
### Rat
\begin{table}
\begin{tabular}{c c c} \hline
**Effects** & **Species** & **References** \\ \hline
**Feeding** & & \\ \hline Central nucleus of the amygdala: orexin A increased gastric motility and palatable food & Rat & [81] \\ intake & & \\ \hline Posterior parauventricular thalamus: regulation of hunger-related signals in nucleus & Rat & [82,83] \\ accumbens core. Sucrose feeding increases dopamine release in nucleus accumbens shell & Rat & [82,83] \\ \hline Chronic intake of fructose: increased orexin A level in hypothalamus and ventral & Rat & [84] \\ tegmental area & & \\ \hline Feeding (rest phase): decrease in the activation of hypothalamic lateral neurons & Rat & [85] \\ expressing orexin & & \\ \hline Decreased orexin A plasma level after four weeks of time-restricted feeding regimen & Mouse & [86] \\ \hline
**Sexual dimorphism** & & \\ \hline Higher demand in females than in males for highly palatable food & Rat & [75] \\ \hline
**Receptors** & & \\ \hline Decrease of sensitivity to gastrointestinal nutrient load and more consumption of & Rat & [87] \\ food-hindbrain orexin 1 receptors & Rat & [88] \\ \hline Administration of sea buckthorn seed oil: increase of orexin A levels and expression of & Rat & [88] \\ orexin 1 receptors in hypothalamus and brainstem & & \\ \hline Orexin 1 receptor-deficient animals resistant to diet-induced obesity and food & Mouse & [89] \\ consumption & & \\ \hline Orexin 2 receptor-deficient animals: less energy expenditure when consumed a high-fat & Mouse & [89] \\ diet & & \\ \hline
**Others** & & \\ \hline Orexinergic system: mediation of age-related deficits in behavioral/neurochemical & Rat & [90] \\ mechanisms of feeding & & \\ \hline Prazosin: motivational response of food consumption through orexinergic system & Rat & [91] \\ \hline Animals lacking dynorphin peptides: decrease in orexin A hypothalamic level & Mouse & [92] \\ \hline Increased orexin hypothalamic expression in pinealectomized animals & Rat & [93] \\ \hline Orexin A: improved glucose control by protecting beta-cells from apoptosis and by & & \\ \hline increasing the sensitivity to insulin & Rat & [94] \\ \hline Bilateral nephrectomized animals: orexin involved in anorexia development & Rat & [95] \\ \hline \end{tabular}
\end{table} 
Table 3: _Cont._on feeding-related nerve cells are dynamic and specific for each type of neuron. However, it was also demonstrated that orexinergic neurons (orexin A) shows an endocannabinoid-mediated disinhibition due to an increase in the inhibitory cannabinoid receptor type 1 positive puncta _versus_ the excitatory ones [96]. In obese animals, the activation of the cannabinoid receptor type 1 decreases the inhibition of the orexinergic neurons and hence increases the release of orexin A, promoting hyperplasia and body weight [96]. The latter study showed that obesity-driven synaptic remodeling affects the endocannabinoid control of neurons containing orexin [96]. It was also reported that a perinatal maternal high-fat diet increases the hypothalamic projections (e.g., from the ventromedial hypothalamus) to the lateral hypothalamus containing neurons expressing orexin A as well as the basal activation of these neurons [41] (Table 3). A responsiveness of lateral hypothalamic neurons to leptin was also observed [41]. Because nerve cells located in the lateral hypothalamus send projections to dopaminergic neurons located in the ventral tegmental area, it seems that these hypothalamic nerve cells are involved in early dietary programming of the mesocorticolimbic reward circuits. In rats, it was reported that the intestinal electrical stimulation modifies the hypothalamic expression of orexin in the lateral hypothalamus and ameliorates diet-induced obesity [77] (Table 3). Electrical stimulation decreases food intake, body weight and the expression of orexin and improves insulin sensitivity and glucose tolerance.