Research reportAssociation between the amygdala and nucleus of the solitary tract in μ-opioid induced feeding in the rat
Introduction
The central nucleus of the amygdala (CNA) and the nucleus of the solitary tract (NTS) are important in many autonomic functions including regulation of ingestive behavior. Lesions of, or opioid agonist administration into either of these brain nuclei result in increased food intake 3, 6, 9, 10, 13, 15, 18, 30, 31. The μ-agonist DAMGO is a potent opioid ligand that increases feeding in both of these brain nuclei 6, 15. Co-administration of naloxone, an opioid antagonist, along with DAMGO into the CNA blocks DAMGO-induced increase in food intake [6]. The effect of this drug combination on food intake has not been evaluated in the NTS. However, central as well as intra-NTS injection of naloxone decreases deprivation-induced feeding and neuropeptide Y (NPY)-induced feeding 14, 16, 19.
There is anatomical evidence that the CNA receives afferent projections from the NTS and that the NTS receives efferent projections from the CNA 11, 21, 28. Petrov et al. [24]reported that electrical stimulation of the CNA induced Fos-like immunoreactivity in the NTS and various hypothalamic nuclei suggesting a neural connection between the CNA and the NTS. It has been suggested that the amygdaloid complex may modulate activity of midbrain and caudal brainstem centers via the hypothalamus 22, 24, 25, 26. In addition to such direct data demonstrating connectivity between the CNA and NTS, other studies have shown that these two nuclei are involved in various physiological events. Ritter and Dinh [29]reported that 2-deoxy-glucose and 2-mercaptoacetate induced Fos-like immunoreactivity in both nuclei, suggesting participation in the metabolic control of feeding. Others have shown that doses of 2,5-anhydro-d-mannitol that reliably stimulate food intake induced Fos-like immunoreactivity in both nuclei as well as other sites [12]. Several reports have also indicated neuronal connection between the CNA and the NTS involving GABAergic neurons as well as μ-opioid receptors in both nuclei 1, 2, 27, 32.
Based on the above data, we evaluated whether an opioid–opioid signaling pathway exists between the CNA and rNTS which affects feeding behavior. To study this interaction, we stimulated feeding by injecting DAMGO into one of these two nuclei and attempted to block feeding by simultaneously injecting the opioid antagonist naltrexone (NTX) into the other site.
Section snippets
Materials and methods
Male Sprague–Dawley rats (Harlan, Madison, WI), weighing 225–250 g, were individually housed in conventional hanging cages with a 12 h light/12 h dark photoperiod (lights on at 0700) in a temperature controlled room (21–22°C). Rats were anesthetized with Nembutal (40 mg/kg) and fitted with 26 gauge stainless steel guide cannula (Plastics One, Austin, TX) in the CNA and/or in the rostral region of the NTS (at the level of the rostral extent of the nucleus ambiguus) (rNTS). Stereotaxic
Results
NTX given 15 min prior administration of DAMGO into the rNTS significantly blocked DAMGO-induced food intake (F2,26=7.82, p=0.004). The 26.5 nmol dose of NTX inhibited DAMGO-induced feeding by approximately 45% compared to the group receiving DAMGO/saline (Fig. 2).
In the second experiment, we found a main effect of drug administration on food intake (F5,65=9.802, p=0.0001). CNA DAMGO increased feeding more than two fold compared to the vehicle-injected rats (p=0.0001) (Fig. 3). When doses of
Discussion
In the present study, we evaluated potential opioid–opioid signaling between two brain sites known to be involved in the regulation of feeding, the rNTS and the CNA. It is known that injection of opioid ligands into either one of these sites increases feeding behavior 7, 8, 15, 16, 17, 18, 20. Blockade of opioid receptors in these sites decreases food intake stimulated by opioids or by food deprivation 6, 15, 16, 19, 31.
As noted by others, we found that DAMGO, a ligand selective for the
Acknowledgements
This research was supported by the General Research Funds of the Veterans Administration Medical Center, the National Institute of Diabetes and Digestive and Kidney Diseases Grant DK 50456 and by the National Institute of Drug Abuse Grant DA-03999. We thank Jim Pomonis and Martha Grace for their technical assistance.
References (32)
- et al.
Ablation of the area postrema causes exaggerated consumption of preferred foods in the rat
Brain Res.
(1981) - et al.
Effect of the opioid antagonist naltrexone on feeding induced by DAMGO in the central nucleus of the amygdala and the paraventricular nucleus in the rat
Brain Res.
(1998) Involvement of m opioid receptors in the amygdala in the control of feeding
Neuropharmacology
(1988)- et al.
The stimulation of food intake by selective agonists of mu, kappa and delta opioid receptors
Life Sciences
(1986) - et al.
Opioid-induced feeding: localization of sensitive brain sites
Brain Research
(1986) - et al.
2,5-Anhydro-d-mannitol induces Fos-like immunoreactivity in hindbrain and forebrain-relationship to eating behavior
Brain Res.
(1998) - et al.
PVN-hindbrain pathway involved in the hypothalamic hyperphagia-obesity syndrome
Physiol. Behav.
(1988) - et al.
Alterations in deprivation, glucoprivic and sucrose intake following general, mu and kappa opioid antagonists in the hypothalamic paraventricular nucleus of rats
Neuroscience
(1995) - et al.
Endorphinergic and alpha-noradrenergic systems in the paraventricular nucleus: effects on eating behavior
Peptides
(1982) - et al.
The effect of centrally administered naloxone on deprivation and drug-induced feeding
Pharmacol. Biochem. Behav.
(1990)
Feeding induced by opiates injected into the paraventricular hypothalamus
Peptides
Projections from the nucleus of the solitary tract in the rat
Neuroscience
Adrenergic projections from the lower brainstem to the hypothalamic paraventricular nucleus, the lateral hypothalamic area and the central nucleus of the amygdala in rats
J. Chem. Neuroanat.
Branching projections of catecholaminergic brainstem neurons to the paraventricular nucleus and the central nucleus of the amygdala in the rat
Brain Res.
Anatomical evidence of direct projections from the nucleus of the solitary tract to the hypothalamus, amygdala and other forebrain structures in the rat
Brain Res.
2-Mercaptoacetate and 2-deoxy-glucose induce fos-like immunoreactivity in rat brain
Brain Res.
Cited by (60)
‘Liking’ and ‘wanting’ in eating and food reward: Brain mechanisms and clinical implications
2020, Physiology and BehaviorPhenotyping neurons activated in the mouse brain during restoration of salt debt
2019, Journal of Chemical NeuroanatomyCitation Excerpt :iNTS neurons may also be a source of this opioid ligand, as we identified that salt consumption also activates enkephalinergic neurons within this region, and a small population of iNTS neurons project to the CeA. In line with this possibility, bi-directional mu opioid receptor signalling between these two structures influences feeding in rats (Giraudo et al., 1998). However, it is also possible that these CeA and iNTS enkephalin neurons project to extra-CeA sites.
Principles of motivation revealed by the diverse functions of neuropharmacological and neuroanatomical substrates underlying feeding behavior
2013, Neuroscience and Biobehavioral Reviews