doi:10.1016/j.bbr.2004.05.021 
Copyright © 2004 Elsevier B.V. All rights reserved.
Research report
Food restriction and leptin impact brain reward circuitry in lean and obese Zucker rats
Stephanie Fultona, 
, 
, Denis Richardb, Barbara Woodsidea and Peter Shizgala
aCenter for Studies in Behavioral Neurobiology, Concordia University, Montréal, Qué., Canada H3G 1M8
bDépartement de Physiologie, Faculté de Médecine, Université Laval, Québec, Que., Canada G1K 7P4
Received 6 March 2003;
revised 2 May 2004;
accepted 3 May 2004.
Available online 10 July 2004.
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Abstract
The rewarding effect produced by electrically stimulating certain sites in the lateral hypothalamus (LH) can be potentiated by food restriction and body weight loss in lean rats. Central leptin and insulin administration can suppress the rewarding impact of the stimulation. To determine whether there are additional peripheral signals that mediate the effect of weight loss on brain reward circuitry, we assessed changes in LH-self-stimulation following food restriction in the obese Zucker rat which develops resistance to circulating leptin and insulin. In addition, we examined the impact of acute food deprivation and leptin administration on LH self-stimulation in lean and obese Zucker rats. The number of brain stimulation rewards earned was measured over a range of LH stimulation frequencies that drove reward rates from zero to asymptotic levels. Restriction reduced frequency thresholds in a subset of lean and obese rats, whereas BSR was unaltered by acute food deprivation. Despite impairment in leptin signaling, intraventricular leptin (4 μg) increased thresholds in most lean and obese rats in which the rewarding effect was sensitive to restriction. These results show that brain reward circuitry in the obese Zucker rat is sensitive to weight loss and leptin.
Keywords: Obesity; Energy balance; Reinforcement; Deprivation; Lateral hypothalamus; Body weight; Resistance
Fig. 1. Effects of chronic food restriction on self-stimulation at LH sites where the rewarding effect of electrical stimulation is either sensitive (A and C) or insensitive (B and D) to chronic food restriction. (A) Rate–frequency curves are shifted leftwards during chronic food restriction (open symbols) with respect to curves obtained during the free-feeding baseline (filled symbols) in a subset of obese rats. (B) In contrast, rate–frequency curves remained stable following chronic food restriction in the remaining obese rats. Each data point is an average of six measures collected on each test day. (C) Magnitude of the curve shifts produced by food restriction in restriction-sensitive obese and lean subjects. (D) Magnitude of the curve shifts produced by food restriction in restriction-insensitive obese and lean rats. M-50 refers to the stimulation frequency required to maintain the half-maximal number of rewards earned. *P ≤ 0.05; **P ≤ 0.005.
Fig. 2. Failure of acute food deprivation to alter self-stimulation in lean and obese rats. (A) Rate–frequency curves obtained following 48-h food deprivation (open symbols) overlap those collected during free-feeding (closed symbols) in an obese rat in which the rewarding effect was sensitive to chronic food restriction. (B) Similarly, food deprivation failed to shift rate–frequency curves in an obese rat in which the rewarding effect was insensitive to chronic food restriction. Each data point is an average of six measures collected on each test day. (C) Magnitude of the curve shifts (ΔM-50) produced by acute food deprivation in obese and lean rats with restriction-sensitive sites. (D) ΔM-50 following acute food deprivation in obese and lean rats with restriction-insensitive sites. *P ≤ 0.05; **P ≤ 0.005.
Fig. 3. Divergent effects of ICV leptin on rewarding effects of LH stimulation. (A) Leptin shifted rate–frequency curves rightward (leptin: open symbols; vehicle control: filled symbols) at a stimulation site in an obese rat that was sensitive to the effects of weight loss (see Fig. 1A). (B) At a stimulation site in an obese rat where chronic restriction failed to enhance the rewarding effect (see Fig. 1B), rate–frequency curves were unchanged after leptin administration. (C) Magnitude of curve shifts (ΔM-50) during the 4 days following ICV leptin in restriction-sensitive obese and lean rats. (D) ΔM-50 during the 4 days following ICV leptin in obese and lean rats with restriction-insensitive sites. PI: post-injection; *P ≤ 0.05; **P ≤ 0.005.
Fig. 4. Effects of a single ICV injection of leptin (4 μg) on food intake for 4 days in obese and lean Zucker rats. Data represent means and SEM. *P ≤ 0.05; **P ≤ 0.005.
Fig. 5. Location of the tips of the stimulation electrodes. Electrodes producing rewarding effects that were enhanced by chronic food restriction are designated by open symbols and electrodes producing rewarding effects that were unaffected by chronic food restriction are designated by closed symbols; the individual rats are identified in Table 1. The coronal sections are based on the atlas of Paxinos and Watson [30].
Table 1.
Symbols marking electrode placements for individual rats
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