Meal Pattern Analysis of Macronutrient Intake Aafter PVN Norepinephrine and Peripheral Clonidine Administration

Abstract

Norepinephrine (NE) injected into the paraventricular nucleus (PVN) of the hypothalamus of rats is a potent stimulant of food intake, more specifically ingestion of the carbohydrate nutrient. In 2 experiments of the present study, this effect was found to be dose-dependent, and the effectiveness of NE in potentiating total food consumption was greatly reduced when the carbohydrate diet was removed. In addition, experiments using a computer-automated data acquisition apparatus were performed to characterize, in detail, the impact of PVN injection of NE and peripheral administration of the alpha2-noradrenergic agonist clonidine (CLON) on the macrostructure of feeding behavior in animals given 3 pure macronutrient diets. These 2 compounds, injected at the onset of the nocturnal feeding cycle, had very similar effects on meal patterns, with both affecting nutrient intake by increasing meal size and duration rather than by increasing meal frequency. They both affected primarily the first meal of the dark cycle, selectively enhancing carbohydrate ingestion by increasing Kcal intake, percent composition in the total diet and feeding time, and also by decreasing the satiating impact of this macronutrient. These stimulatory effects of NE and CLON on carbohydrate ingestion during the first meal were followed by complete recovery over the next 1 to 2 hours after injection. In addition to these predominant effects on carbohydrate intake, PVN NE at the highest doses tested (10 and 20 nmoles) produced a small increase in fat intake, whereas peripheral CLON actually decreased intake of fat and protein over the 12-hour cycle. The similarities in the impact of NE and CLON on carbohydrate feeding patterns support the hypothesis that both agonists may be acting via the same PVN alpha2-noradrenergic system controlling ingestion of the carbohydrate-rich meals which predominate at dark onset.

Paraventricular hypothalamic nucleus: Axonal projections to the brainstem

“…Microinjection mapping studies identified the PVH as the most sensitive site in the brain for the increase in feeding behavior produced by alpha‐adrenergic agonists like norepinephrine or clonidine (Leibowitz,1978) and by neuropeptide Y (NPY; Stanley and Leibowitz,1985). Increased feeding can begin within seconds to minutes after injection of norepinephrine (Leibowitz,1978), but the primary effect is an increase in meal size, not frequency (Ritter and Epstein,1975; Leibowitz et al,1993). All the receptors implicated in these feeding responses—the α2‐adrenoreceptor for norepinephrine/epinephrine (Goldman et al,1985), and the Y1 and Y5 receptors for NPY (Kalra et al,1991; Gerald et al,1996)—are coupled to inhibitory G‐proteins (G αi ), which reduce neuronal activity by inhibiting cAMP synthesis (Dohlman et al,1991).…”

Short-term sympathoadrenal inhibition augments the thermogenic response to β-adrenergic receptor stimulation

“…3 kg). In addition to decreased EE, this weight gain may be attributable to fluid retention (Morrison et al 1990, Laurent & Safar 1992, and perhaps also increased dietary intake (Leibowitz et al 1993, Rieg & Aravich 1994, Delgado-Aros & Camilleri 2005.…”

Central Sympathetic Modulation Reverses Microvascular Alterations in a Rat Model of High‐Fat Diet‐Induced Metabolic Syndrome

“…Moxonidine, another second generation centrally acting antihypertensive agent acting on I 1 Rs, also induces reduction in food intake in the obese spontaneously hypertensive rat . Notwithstanding, clonidine is known to increase food intake via the stimulation of systemic or central α 2 Rs. In our experimental model of diet‐induced MS, chronic treatment with clonidine induced a reduction in food intake.…”