Glutamate receptors in the nucleus accumbens shell control feeding behavior via the lateral hypothalamus

Abstract

The nucleus accumbens in a brain region considered to be important in the regulation of appetitive behavior and reinforcement. The accumbens receives afferent input from corticolimbic and thalamic structures, which is primarily coded by excitatory amino acids (EAAs). The present studies investigated the role of EAA input to the nucleus accumbens in feeding behavior in rats, in two recently characterized subregions of the accumbens, the "core" and "shell". In the first series of experiments, it was shown that blockade of alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) and kainate glutamate receptors in the medial part of the accumbens, corresponding to the medial shell subregion, resulted in a pronounced feeding response. Bilateral microinfusion of 6,7-dinitroquinoxaline-2,3-dione (DNQX, 0.25-0.75 micrograms/0.5 microliters), 6-cyano-7-nitroquinoxaline (CNQX, 0.75-1.5 micrograms), and 2,3-dihydroxy-6-nitro-7-sulfamoylbenzo-(F) quinoxaline (NBQX, 0.2-1.0 micrograms) markedly stimulated food intake immediately following infusion, in a dose-dependent manner. Infusion of DNQX into the central accumbens region, corresponding to the core, did not elicit feeding. Infusion of the NMDA antagonists 2-amino-5-phosphonopentanoic acid (AP-5) and MK-801 (dizocilpine maleate) did not elicit feeding in either region. The feeding response to DNQX was blocked by local coinfusion of AMPA. Systemic pretreatment with naltrexone (5 mg/kg) had no effect on the DNQX-feeding response; however, prior systemic administration of both D-1 and D-2 antagonists reduced the response by half, suggesting a modulatory role for dopamine in the response. Moreover, the feeding response was completely inhibited by concurrent infusion of the GABAA agonist muscimol (10, 25 ng) into the lateral hypothalamus, a major projection area of the accumbens shell. These findings demonstrate a selective role for non-NMDA receptors in the nucleus accumbens shell in ingestive behavior, and suggest an important functional link between two major brain regions involved in reward, the nucleus accumbens and lateral hypothalamus.

Zonisamide Prevents Olanzapine-Associated Hyperphagia, Weight Gain, and Elevated Blood Glucose in Rats

“…The antiepileptic activity of ZNS may be mediated by a decreased production of GABA transporters, resulting in increased tissue and synaptic concentrations of GABA and enhanced GABA mediated neuronal inhibition (Czapinski et al, 2005). ZNS is also thought to potentially inhibit glutamate mediated neuronal excitation (Maldonado-Irizarry et al, 1995). This may explain our finding that ZNS attenuated the degree of OLZ-associated Fos-LI in the nucleus accumbens.…”

A novel procedure for assessing the effects of drugs on satiation in baboons: effects of memantine and dexfenfluramine

“…A large series of studies demonstrated a role for glutamate in meal size using localized microinfusions in brain areas associated with feeding or reinforcement (e.g., Zeni et al 2000). Infusions of glutamate in the Nucleus Accumbens decreased food intake, while infusions of glutamate antagonists in the Nucleus Accumbens increased food intake by increasing meal size rodents (Maldonado-Irizarry et al 1995;Stratford et al 1998;Zeni et al 2000), and central infusions of glutamate agonists and antagonists in the pigeon produced a similar pattern of results (Da Silva et al 2006;Gillespie et al 2005). Several studies have also shown that peripheral administration of the NMDA non-competitive antagonist (+)MK-801 (dizocilpine) also increased meal size in the rat (Treece et al 2000;Jahng and Houpt 2001), perhaps due to an increase in the rate of gastric emptying (Covasa et al 2000).…”

Orexin in Rostral Hotspot of Nucleus Accumbens Enhances Sucrose ‘Liking’ and Intake but Scopolamine in Caudal Shell Shifts ‘Liking’ Toward ‘Disgust’ and ‘Fear’

“…Conversely, in caudal shell, agonist microinjections reveal a 'hedonic coldspot', where opioid stimulation suppresses sucrose hedonic impact (Castro and Berridge, 2014;Pecina and Berridge, 2005). By contrast to the localized hotspot for sweetness 'liking', mu-opioid stimulations increase motivation to eat much more widely and homogeneously throughout the entire NAc shell (and in related structures), measured as increases in cue-triggered 'wanting' to obtain food rewards (eg, in instrumental breakpoint and pavlovian-instrumental transfer tests), as well as in food consumption (Castro and Berridge, 2014;Covelo et al, 2014;Maldonado-Irizarry et al, 1995;Pecina and Berridge, 2005;Pecina and Berridge, 2013;Smith and Berridge, 2005;Smith et al, 2011;Zhang and Kelley, 2000).…”