Research report
Specific changes in food intake elicited by blockade or activation of glutamate receptors in the nucleus accumbens shell

https://doi.org/10.1016/S0166-4328(97)00140-XGet rights and content

Abstract

Blockade of non-N-methyl-D-aspartic acid (NMDA) ionotropic glutamate receptors in the nucleus accumbens shell (AcbSh) with 6,7-dinitroquinoxaline-2,3-dione (DNQX) elicits intense feeding in satiated rats. In order to determine whether or not this feeding is part of a general behavioral activation, we observed the effect of intra-AcbSh DNQX injections on intake of solid food, liquid food, and water, and on gnawing behavior. In addition, we investigated the possibility that activation of a subset of these receptors with (±)-α-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) could suppress feeding. DNQX significantly increased intake of solid and liquid food, but did not significantly affect water intake or gnawing behavior. Furthermore, injections of AMPA into the AcbSh suppressed deprivation-induced feeding and intake of a palatable 5% sucrose solution without affecting water intake in water-deprived rats. Taken together, these data suggest that DNQX is acting on a system specifically involved with the regulation of food intake.

Introduction

The nucleus accumbens (Acb) is a basal forebrain structure that perhaps is known best for the critical role it plays in reinforcement processes 15, 25. However, there is an accumulating body of evidence that suggests it also may be an important component of a neural system mediating feeding behavior. Several studies have investigated the role that opioid and dopamine systems located in the nucleus accumbens play in the control of food intake. Injections of opioid agonists into the Acb have been shown to increase food intake in non-deprived rats 2, 17, 20, 32and injections of opioid receptor antagonists into this region can suppress feeding elicited by deprivation, glucoprivation, presentation of a palatable sucrose solution, or by injection of 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) into the rostral raphe nuclei 4, 11. In contrast, the contribution of Acb dopamine to the control of food intake is more equivocal. Intra-Acb administration of amphetamine has been reported variously to decrease food intake [7], to have no effect on food intake [13], or to increase or decrease food intake depending on dose [9]and individual baseline intake [29]. Injections of D1 and/or D2 receptor family agonists do not significantly affect food intake [22], but injection of a specific D3 receptor agonist has been reported to decrease intake of a sucrose solution, probably through its effects on presynaptic autoreceptors [12]. Although injections of dopamine antagonists into the Acb have been shown to suppress feeding elicited by electrical stimulation of the medial forebrain bundle [19], by systemic administration of a low dose of amphetamine [28], or by injections of 8-OH-DPAT [10]or muscimol [3]into the rostral raphe nuclei, selective dopamine-depleting lesions of the Acb do not appear to affect ad lib food intake significantly 16, 26, 35. Thus, at this time the exact nature of the role of Acb dopamine in the control of food intake remains unclear.

More recently, the role played by Acb excitatory and inhibitory amino acids in the control of food intake has been investigated. Inhibition of cells in the shell subregion of the Acb (AcbSh) by administration of non-NMDA ionotropic glutamate antagonists [18]or γ-aminobutyric acid (GABA) agonists [30]greatly increases food intake in satiated rats. The very short latency to feed and large intake seen after manipulations of AcbSh glutamate and GABA receptors demonstrate that these amino acids are components of a neural system that is capable of profoundly influencing feeding behavior in the rat. Still, it is possible that inhibiting cells in the AcbSh does not specifically activate feeding behavior, but rather elicits a general behavioral activation that results in an increased tendency to engage in a variety of stimulus-bound oral behaviors, such as eating food, drinking water, and gnawing non-food items. This type of general increase in ingestive-related behaviors can be elicited by electrical stimulation of the lateral hypothalamus 23, 24, 33or the midbrain [34], by injection of opioid agonists into the ventral tegmental area [1], and by inhibition of cells in the median raphe nucleus 14, 36, 37.

In the current study, we investigated the specificity of the role played by AcbSh glutamate receptors in the control of food intake. To that end, we compared the effect of blocking AMPA and kainate receptors with DNQX on intake of both solid and liquid foods, as well as on water intake and gnawing behavior. Furthermore, because blocking AMPA and kainate receptors initiates feeding in satiated rats, we hypothesized that administration of exogenous AMPA might suppress feeding in rats predisposed to do so. Therefore, to help characterize further the ability of AcbSh glutamate receptors to control food intake, we also investigated the effect of activating AcbSh AMPA receptors on feeding in food-deprived rats or rats presented with a palatable sucrose solution. Portions of this study have appeared previously in abstract form [31].

Section snippets

Animals

Male Sprague–Dawley rats (Harlan) weighing between 280 and 300 g at the time of surgery were group housed in acrylic cages and maintained in a temperature-controlled (∼21°C) and light-controlled (12 h light:12 h dark) environment with food (Harlan Teklad Rat Diet 7001) and acidified tap water available ad libitum.

Surgery

The rats were anesthetized with a mixture of ketamine HCl and xylazine HCl (100 mg/kg and 10 mg/kg, respectively; Sigma Chemical Co., St. Louis, MO) and bilateral 23-gauge stainless

Histology

The targeted and acceptable injection sites were the ventromedial AcbSh. Data from rats with misplaced cannulae were not included in the statistical analyses. Although AMPA can be neurotoxic in some cases, there was no visible evidence of excessive local damage after injections of 10 and 50 ng of AMPA into this brain region. A schematic diagram of a typical injection site is presented in Fig. 1.

Ingestive behavior

DNQX significantly increased 30 min food intake (t(8)=8.0, P<0.0001) without affecting water intake (

Discussion

With this series of studies we have demonstrated that blockade of AMPA and kainate receptors in the shell of the nucleus accumbens specifically increases food intake in rats. After intra-AcbSh injections of DNQX, rats ate significantly more solid or liquid food, but did not change the amount of water ingested or the amount of time spent gnawing wooden blocks. Even when the rats were dehydrated and predisposed to drink, DNQX did not affect water intake when water was presented alone. When food

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