GABA receptor subtype antagonists in the nucleus accumbens shell and ventral tegmental area differentially alter feeding responses induced by deprivation, glucoprivation and lipoprivation in rats

Brain Res. 2006 Apr 12;1082(1):86-97. doi: 10.1016/j.brainres.2006.01.112. Epub 2006 Mar 6.

Abstract

GABA(A) and GABA(B) receptor agonists stimulate feeding following microinjection into the nucleus accumbens shell and ventral tegmental area, effects blocked selectively and respectively by GABA(A) and GABA(B) receptor antagonists. GABA antagonists also differentially alter opioid-induced feeding responses elicited from these sites. Although GABA agonists and antagonists have been shown to modulate feeding elicited by deprivation or glucoprivation, there has been no systematic examination of feeding elicited by homeostatic challenges following GABA antagonists in these sites. Therefore, the present study examined the dose-dependent ability of GABA(A) (bicuculline, 75-150 ng) and GABA(B) (saclofen, 1.5-3 microg) antagonists administered into the nucleus accumbens shell or ventral tegmental area upon feeding responses elicited by food deprivation (24 h), 2-deoxy-D-glucose-induced glucoprivation (500 mg/kg) or mercaptoacetate-induced lipoprivation (70 mg/kg). A site-specific effect of GABA receptor antagonism was observed for deprivation-induced feeding in that both bicuculline and saclofen administered into the nucleus accumbens shell, but not the ventral tegmental area, produced short-term (1-4 h), but not long-term (24-48 h) effects upon deprivation-induced intake without meaningfully altering body weight recovery. In contrast to the relative inability of GABA receptor antagonism in both sites to alter 2-deoxy-D-glucose-induced intake, mercaptoacetate-induced intake was eliminated by saclofen and significantly reduced by bicuculline in the nucleus accumbens shell and eliminated by both bicuculline and saclofen in the ventral tegmental area. These data reinforce the findings that GABA(A) and GABA(B) receptors in the nucleus accumbens shell and ventral tegmental area are not only important in the modulation of pharmacologically induced feeding responses, but also participate in differentially mediating the short-term feeding response to food deprivation in the nucleus accumbens shell as well strongly modulating lipoprivic, but not glucoprivic feeding responses in both sites.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Baclofen / analogs & derivatives*
  • Baclofen / pharmacology
  • Behavior, Animal
  • Bicuculline / pharmacology*
  • Body Weight / drug effects
  • Deoxyglucose / pharmacology
  • Dose-Response Relationship, Drug
  • Drug Interactions
  • Eating / drug effects
  • Feeding Behavior / drug effects*
  • Feeding Behavior / physiology
  • Food Deprivation / physiology*
  • GABA Antagonists / pharmacology*
  • Glucose / deficiency
  • Lipids / deficiency
  • Male
  • Nucleus Accumbens / drug effects*
  • Rats
  • Rats, Sprague-Dawley
  • Thioglycolates / pharmacology
  • Time Factors
  • Ventral Tegmental Area / drug effects*

Substances

  • GABA Antagonists
  • Lipids
  • Thioglycolates
  • 2-mercaptoacetate
  • Deoxyglucose
  • Baclofen
  • Glucose
  • saclofen
  • Bicuculline