Ventral tegmental area infusion of substance P, neurotensin and enkephalin: Differential effects on feeding behavior

doi:10.1016/0306-4522(86)90061-8

Neuroscience

Volume 18, Issue 3, July 1986, Pages 659-669

https://doi.org/10.1016/0306-4522(86)90061-8 Get rights and content

Abstract

The neuropeptides substance P, neurotensin and [Met]enkephalin are found in the ventral tegmental area, site of the A10 dopamine cell bodies. Evidence suggests a functional interaction between these peptides and the dopaminergic neurons. All three peptides have been shown to exert an activating effect on these neurons. The present study analyzed the effects of ventral tegmental area infusion of neurotensin, substance P and d-ala-[Met]enkephalin on feeding behavior. These effects were studied in both food-deprived and satiated rats. During a 30 min test, the following parameters were registered: latency to eat, total food intake, food spillage, number of eating bouts and duration of eating. Similar measures were taken for drinking. In deprived rats substance P (0.5, 3.0μg) increased latency to eat but did not affect other parameters, and substance P did not affect eating in satiated rats. Neurotensin (0.5, 2.5 μg) increased latency to eat and markedly reduced food consumption in deprived rats and had no effect in satiated rats. d-Ala-[Met]enkephalin (0.1, 1.0 μg) stimulated feeding behavior in both deprived and satiated rats. These results show that although the different peptides are presumed to activate the dopaminergic A10 neurons, their effects on feeding behavior can be differentiated. The findings are discussed in terms of motor and motivational mechanisms, and the relative contributions of specific and non-specific influences on feeding are considered.

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Dopamine (DA) neurons in the ventral tegmental area (VTA) modulate physical activity and feeding behaviors that are disrupted in obesity. Yet, the heterogeneity of VTA DA neurons has hindered determination of which ones might be leveraged to support weight loss. We hypothesized that increased activity in the subset of VTA DA neurons expressing neurotensin receptor-1 (NtsR1) might promote weight loss behaviors. To test this, we used Designer Receptors Exclusively Activated by Designer Drugs (DREADDs) to activate VTA NtsR1 neurons in normal weight and diet-induced obese mice. Acute activation of VTA NtsR1 neurons (24hr) significantly decreased body weight in normal weight and obese mice by reducing food intake and increasing physical activity. Moreover, daily activation of VTA NtsR1 neurons in obese mice sustained weight loss over 7 days. Activating VTA NtsR1 neurons also suppressed how much mice worked to obtain sucrose rewards, even when there was high motivation to consume. However, VTA NtsR1 neural activation was not reinforcing, nor did it invoke liabilities associated with whole-body NtsR1 agonism such as anxiety, vasodepressor response or hypothermia. Activating VTA NtsR1 neurons therefore promotes dual behaviors that support weight loss without causing adverse effects, and is worth further exploration for managing obesity.
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^∗: Present address: Department of Psychology and Social Relations, Harvard University, William James Hall, Cambridge, MA 02138, U.S.A.

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Ventral tegmental area infusion of substance P, neurotensin and enkephalin: Differential effects on feeding behavior

Abstract

Neurosci. Lett.

Brain Res.

Behav. Brain Res.

Brain Res.

Neuropharmacology

Brain Res.

Brain Res.

Neurosci. Lett.

Neurosci. Lett.

Peptides

Pharmac. Biochem. Behav.

Neuroscience

Eur. J. Pharmac.

Life Sci.

Life Sci.

Neurosci. Biobehav. Rev.

Pharmac. Biochem. Behav.

Life Sci.

Neuropharmacology

Peptides

Brain Res.

Peptides

Appetite

Brain Res.

Life Sci.

Brain Res.

Brain Res.

Neurotensin selectively activates dopaminergic neurons of the substantia nigra

Soc. Neurosci. Abstr.

Role of endogenous substance P in stress-induced activation of mesocortical dopamine neurons

Nature

Do enkephalin systems mediate drive reduction?

Soc. Neurosci. Abstr.

Intracranial self-administration of morphine into the ventral tegmental area

Life Sci.

Stimulant effects of enkephalin microinjection into the dopaminergic A10 area

Nature