Mercaptoacetate-induced feeding is impaired by central nucleus of the amygdala lesions

doi:10.1016/0031-9384(95)02050-0

Physiology & Behavior

Volume 58, Issue 6, December 1995, Pages 1215-1220

https://doi.org/10.1016/0031-9384(95)02050-0 Get rights and content

Abstract

Systemic administration of mercaptoacetate (MA) blocks beta oxidation of fatty acids and stimulates food intake. The present experiment examined MA-induced feeding in rats with bilateral lesions of the central nucleus of the amygdala (CNA) and sham-operated controls. Food intake was measured for 6 h immediately following IP injection of 400, 600, or 800 μmol/kg of MA or saline. Feeding was also measured in these rats in response to 2-deoxy-D-glucose (2DG) (100, 200, and 300 mg/kg, SC), a glucose analogue that competitively inhibits glucose utilization. We found that CNA lesions blocked feeding in response to all three doses of MA. Feeding in response to 2DG was significantly reduced, but not abolished, by the lesion. These findings suggest that the CNA is a crucial component of the neural pathway for feeding in response to MA and may also participate in 2DG-induced feeding.

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Basolateral amygdala (BLA) principal cells are capable of driving and antagonizing behaviors of opposing valence. BLA neurons project to the central amygdala (CeA), which also participates in negative and positive behaviors. However, the CeA has primarily been studied as the site for negative behaviors, and the causal role for CeA circuits underlying appetitive behaviors is poorly understood. Here, we identify several genetically distinct populations of CeA neurons that mediate appetitive behaviors and dissect the BLA-to-CeA circuit for appetitive behaviors. Protein phosphatase 1 regulatory subunit 1B⁺ BLA pyramidal neurons to dopamine receptor 1⁺ CeA neurons define a pathway for promoting appetitive behaviors, while R-spondin 2⁺ BLA pyramidal neurons to dopamine receptor 2⁺ CeA neurons define a pathway for suppressing appetitive behaviors. These data reveal genetically defined neural circuits in the amygdala that promote and suppress appetitive behaviors analogous to the direct and indirect pathways of the basal ganglia.
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Olfactory bulbectomy increases prepro-galanin mRNA levels in the locus coeruleus of rats (Holmes and Crawley, 1996) and increases prepro-neuropeptide Y levels in the hypothalamus (Primeaux et al., 2007). Lesions of the central and medial nuclei of the amygdala also abolish the feeding response to 2-DG and other glucoprivic challenges (King, 2006; King et al., 1998; Ritter and Hutton, 1995; Tordoff et al., 1982; see also King et al., 1993), and those nuclei receive projections from the olfactory bulbs and then project to hypothalamic nuclei (de Olmos, 1972; Lammers, 1972). Olfactory bulbectomy affects both serotonergic and prepro-neuropeptide Y activity in the amygdala (Primeaux et al., 2007; Rutkoski et al., 2002; van der Stelt et al., 2005).
An early study reported that, unlike sham-operated rats, rats made anosmic by olfactory bulbectomy (OBX) failed to compensate for the dilution of their diet with nonnutritive bulk by increasing their food intake. In the present study, the effects of a glucoprivic challenge, intraperitoneal-administered 350 mg/kg 2-deoxy-d-glucose (2-DG), on food intake were measured in OBX and sham-operated female rats. Sham-operated rats significantly increased their food intake, but in two separate experiments OBX rats displayed no increase in food intake during the first 2 h following administration. Blood glucose levels were nearly identical in both groups. Body weights and daily food intakes of OBX rats did not differ from the sham-operated controls throughout the studies. Bulbectomized rats also displayed a normal drinking response after an intraperitoneal injection of 1 M hypertonic saline. Hypothalamic nuclei and the neural pathways mediating taste have been implicated in the feeding response to 2-DG. The present results suggest that olfactory input and olfactory neural pathways also mediate, at least in part, the feeding response to a glucoprivic challenge induced by intraperitoneal injection of 2-DG.
Inhibition of fatty acid oxidation activates transforming growth factor-beta in cerebrospinal fluid and decreases spontaneous motor activity
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Intravenous administration of MA induced c-Fos expression in several regions including, NTS, hypothalamus, lateral parabrachial nucleus (IPBN), and the central nucleus of amygdala (CNA). [31]. The lesion of NTS, IPBN and CNA abolish the MA-induced appetite feeding behavior. [10,30,32]. Additionally, the finding that MA-induced feeding behavior is abolished in decerebrate rats indicates that the projection from NTS to forebrain is important for the feeding behavior induced by the inhibition of FA oxidation [11].
We have previously reported that transforming growth factor (TGF)-beta in the cerebrospinal fluid (CSF) is involved in the mechanism underlying the regulation of spontaneous motor activity (SMA) by the central nervous system after exercise. However, it remained unclear what physiological condition triggers the activation of TGF-beta. We hypothesized that the shortage of energy derived from fatty acid (FA) oxidation observed in the early phase of exercise activated TGF-beta in the CSF. To test this hypothesis, we investigated whether mercaptoacetate (MA), an inhibitor of FA oxidation, could induce an activation of TGF-beta in the CSF and a decrease in SMA. Intraperitoneal (i.p.) administration of MA activated TGF-beta in CSF in rats and depressed SMA; 2-deoxyglucose, an inhibitor of carbohydrate oxidation, on the other hand, depressed SMA but failed to activate CSF TGF-beta. Intracisternal administration of anti-TGF-beta antibody abolished the depressive effect of MA on SMA. We also found that the depression of SMA and the activation of TGF-beta in the CSF by i.p. MA administration were eliminated by vagotomy. Our data suggest that TGF-beta in the CSF is activated by the inhibition of FA oxidation via the vagus nerve and that this subsequently induces depression of SMA.
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Glucocorticoids have major effects on food intake, however, the underlying mechanisms are poorly understood. This article highlights data on the changes that occur when glucocorticoids are removed by adrenalectomy, and the effects of central and systemic administered glucocorticoids on feeding behavior in rats. Next, animal data on the interaction of glucocorticoids with insulin on intake of comfort foods are addressed and the hypothesis that glucocorticoids modify feeding behavior, whereas insulin modifies the choice of food is discussed. Finally a view is presented that hormonal and vagal signals generated when (comfort) food is consumed will affect the corticotropin-releasing factor (CRF) brain network important for the response to stress and the regulation of feeding. With a society, where stress is experienced daily and comfort food is found at every street corner, it will be vital to understand the interactions between the systems that react to stress and regulate feeding behavior to fight the obesity epidemic.
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The feeding response following administration of the free fatty acid oxidation inhibitor, mercaptoacetate (MA) is conceptualized as an experimental model of lipoprivation, which may contribute to the understanding of inter-individual differences in the modulation of this homeostatic response. Although variation in the intake of food, water and glucoprivation as well as intake of several nutrients is known to be associated with genetic variation, it is not known whether MA-induced feeding is similarly dependent upon genotype. The present study therefore examined MA-induced feeding in mice of 11 inbred (A/J, AKR/J, BALB/cJ, CBA/J, C3H/HeJ, C57BL6/J, C57BL10/J, DBA/2J, SJL/J, SWR/J, 129P3/J) and one outbred (CD-1) strains across a wide range of previously determined effective MA doses (5, 35, 70, 100 mg/kg) and test times (1–4 h). MA produced significant dose-dependent and strain-dependent increases in food intake with strong responses noted in DBA/2J, outbred CD-1 and AKR/J mice. More limited dose-specific increases in food intake following MA occurred in C3H/HeJ, BALB/cJ, CBA/J, SJL/J, SWR/J and C57BL/6J mice. In contrast, MA failed to significantly increase food intake in A/J, C57BL/10J and 129P/3J mice. MA-induced food intake correlated significantly across strains only following the two highest doses, and intake following only the highest MA dose correlated significantly across strains with intake following only a moderate glucoprivic dose of 2-deoxy-d-glucose. Thus, these inter-strain differences suggest that lipoprivic (e.g., MA intake) and glucoprivic (e.g., 2-deoxy-d-glucose intake) responsivity operate via only partially overlapping genetic mechanisms of action. The demonstration of genotype-dependent variability in this lipoprivic response may provide the basis for the subsequent identification of trait-relevant genes.

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ArticleMercaptoacetate-induced feeding is impaired by central nucleus of the amygdala lesions

Abstract

Peptides

Brain Res.

Brain Res. Rev.

Brain Res. Bull.

Physiol. Behav.

Peptides

J. Autonom. Nerv. Syst.

Brain Res.

Neuroscience

Brain Res.

Brain Res.

Brain Res.

Physiol. Behav.

Physiol. Behav.

J. Biol. Chem.

Inhibition in vitro of acyl-CoA-dehydrogenases by 2-mercaptoacetate in rat liver mitochondria

Biochem. J.

Lesions of specific lateral parabrachial subnuclei abolish feeding induced by mercaptoacetate but not by 2-deoxy-D-glucose

Am. J. Physiol.

Galanin antagonists block galainin-induced feeding in the hypothalamus and amygdala of the rat

Eur. J. Neurosci.

Article
Mercaptoacetate-induced feeding is impaired by central nucleus of the amygdala lesions