Norepinephrine, clonidine, and tricyclic antidepressants selectively stimulate carbohydrate ingestion through noradrenergic system of the paraventricular nucleus.

Using a self-selection feeding procedure, the present experiments examined the impact of central and peripheral injection of the alpha-adrenergic agonist clonidine (CLON) and the tricyclic antidepressant drugs amitriptyline (AMIT) and chlorimipramine (CIMIP) on nutrient selection in the adult male rat. In tests with mixed diets or with separate sources of the 3 macronutrients (carbohydrate, protein, and fat) simultaneously available, the following results were obtained: Peripheral and paraventricular nucleus (PVN) injection of CLON stimulated total food intake and preferentially increased ingestion of carbohydrate. Little or no change in protein or fat intake was observed. This pattern of response is similar to that observed with norepinephrine. PVN injection of AMIT and peripheral injection of CIMIP also selectively enhanced carbohydrate intake. These drug effects on carbohydrate selection occurred under a variety of conditions, including with mixed diets and pure dietary nutrients; under ad lib and restricted feeding conditions; in short (1 hr) as well as long (6 hr) test intervals; and in the absence or presence of a change in total calorie intake. Based on this and other evidence, it is proposed that noradrenergic neurons innervating the PVN in the rat play a role in regulating carbohydrate selection, and that this neurochemical system mediates the stimulating action of CLON and antidepressants on carbohydrate ingestion.

Noradrenergic innervation of the paraventricular nucleus: specific role in control of carbohydrate ingestion.

Acute injections of norepinephrine (NE) into the hypothalamic paraventricular nucleus (PVN) have been shown to elicit eating in satiated rats. The present report examines the effects of acute and chronic PVN infusion of NE on intake of various liquid and mixed solid diets and on selection of the pure macronutrients, carbohydrate, protein, and fat. The results demonstrate that noradrenergic stimulation of the PVN (40 nmoles of NE) reliably enhances ingestion of pure sucrose diets (liquid and solid) and also of sweet and non-sweet milk solutions. Saccharin intake, in contrast, is unaffected. In preference tests, rats injected with NE show a greater increase in consumption of sucrose cubes compared with lab chow pellets, but exhibit an equivalent preference for sweet and non-sweet carbohydrate-rich diets. Tests with the three pure macronutrients simultaneously available reveal, after NE injection, a strong and selective increase in consumption of carbohydrate, with little or no change in intake of fat and, in some cases, a suppression of protein intake. This clear preference for carbohydrate can be seen with chronic NE infusion (5 nmoles every 30 min over a 14-day period), as well as after acute NE injection (40 nmoles), and also with long-term (24-hr) as well as short-term (1-hr) food intake measurements. This and other evidence suggests that the PVN noradrenergic system may play a specific and unique role in the control of carbohydrate ingestion.