GABA in the nucleus accumbens shell participates in the central regulation of feeding behavior - PubMed (original) (raw)

GABA in the nucleus accumbens shell participates in the central regulation of feeding behavior

T R Stratford et al. J Neurosci. 1997.

Abstract

We have demonstrated previously that injections of 6, 7-dinitroquinoxaline-2,3-dione into the nucleus accumbens shell (AcbSh) elicits pronounced feeding in satiated rats. This glutamate antagonist blocks AMPA and kainate receptors and most likely increases food intake by disrupting a tonic excitatory input to the AcbSh, thus decreasing the firing rate of a population of local neurons. Because the application of GABA agonists also decreases neuronal activity, we hypothesized that administration of GABA agonists into the AcbSh would stimulate feeding in satiated rats. We found that acute inhibition of cells in the AcbSh via administration of the GABAA receptor agonist muscimol or the GABAB receptor agonist baclofen elicited intense, dose-related feeding without altering water intake. Muscimol-induced feeding was blocked by coadministration of the selective GABAA receptor blocker bicuculline, but not by the GABAB receptor blocker saclofen. Conversely, baclofen-induced feeding was blocked by coadministration of saclofen, but was not affected by bicuculline. Furthermore, we found that increasing local levels of GABA by administration of a selective GABA-transaminase inhibitor, gamma-vinyl-GABA, elicited robust feeding in satiated rats, suggesting a physiological role for endogenous AcbSh GABA in the control of feeding. A mapping study showed that although some feeding can be elicited by muscimol injections near the lateral ventricles, the ventromedial AcbSh is the most sensitive site for eliciting feeding. These findings demonstrate that manipulation of GABA-sensitive cells in the AcbSh can have a pronounced, but specific, effect on feeding behavior in rats. They also constitute the initial description of a novel and potentially important component of the central mechanisms controlling food intake.

PubMed Disclaimer

Figures

Fig. 1.

Fig. 1.

Mean (±SEM) 30 min food intake after bilateral microinjections of various doses of GABA agonists and antagonists into the AcbSh. a, Intake was increased significantly with all doses of baclofen tested and with all doses of muscimol over 88 pmol. b, As demonstrated in the previous experiment, injection of 188 ng of baclofen significantly increased food intake (p < 0.01). The baclofen-induced feeding was eliminated by coadministration of 500 ng of the selective GABAB antagonist saclofen, but was not affected by 75 ng of the GABAA antagonist bicuculline. c, In a separate group of rats, 50 ng of muscimol significantly increased food intake (p < 0.01), and this increase was abolished by coadministration of 75 ng of bicuculline. Coadministration of 500 ng saclofen had no effect on the feeding elicited by muscimol. Symbols denote significant increases in intake as compared with saline treatment. *p < 0.05; †p < 0.01; ‡p < 0.001.

Fig. 2.

Fig. 2.

Mean (±SEM) food and water intake after injection of various doses of muscimol into the AcbSh. Muscimol dose-dependently increased food intake at all doses >10 ng, with 60–70% of the feeding occurring in the initial 30 min. Muscimol had no effect on 120 min water intake at any dose. *p < 0.05; †p < 0.01.

Fig. 3.

Fig. 3.

Mean (±SEM) food intake after injections of the GABA-T inhibitor GVG or the GABA reuptake inhibitor nipecotic acid into the AcbSh. Although GVG significantly increased food intake at both doses tested (†p < 0.01), nipecotic acid had no effect on feeding behavior.

Fig. 4.

Fig. 4.

Mean (±SEM) food intake after injections of saline or 50 ng of muscimol into the AcbSh and several surrounding sites. Although muscimol injections near the lateral ventricles increased food intake, the ventromedial AcbSh was the most sensitive site for eliciting feeding. †p < 0.01; ‡p < 0.001.

Similar articles

Cited by

References

    1. Bakshi VP, Kelley AE. Feeding induced by opioid stimulation of the ventral striatum: role of opiate receptor subtypes. J Pharmacol Exp Ther. 1993a;265:1253–1260. - PubMed
    1. Bakshi VP, Kelley AE. Striatal regulation of morphine-induced hyperphagia: an anatomical mapping study. Psychopharmacology. 1993b;111:207–214. - PubMed
    1. Beck CH, Fibiger HC. Conditioned fear-induced changes in behavior and in the expression of the immediate early gene c-fos: with and without diazepam pretreatment. J Neurosci. 1995;15:709–720. - PMC - PubMed
    1. Blackburn JR, Phillips AG, Jakubovic A, Fibiger HC. Dopamine and preparatory behavior. II. A neurochemical analysis. Behav Neurosci. 1989;103:15–23. - PubMed
    1. Bodnar RJ, Glass MJ, Ragnauth A, Cooper ML. General, μ and k opioid antagonists in the nucleus accumbens alter food intake under deprivation, glucoprivic and palatable conditions. Brain Res. 1995;700:205–212. - PubMed

Publication types

MeSH terms

Substances

LinkOut - more resources