Exposure to elevated levels of dietary fat attenuates psychostimulant reward and mesolimbic dopamine turnover in the rat

Abstract

Recent studies indicate that decreased central dopamine is associated with diet-induced obesity in humans and in animal models. In the current study, the authors assessed the hypothesis that diet-induced obesity reduces mesolimbic dopamine function. Specifically, the authors compared dopamine turnover in this region between rats fed a high-fat diet and those consuming a standard low-fat diet. The authors also assessed behavioral consequences of diet-induced obesity by testing the response of these animals in a conditioned place paradigm using amphetamine as a reinforcer and in an operant conditioning paradigm using sucrose reinforcement. Results demonstrate that animals consuming a high-fat diet, independent of the development of obesity, exhibit decreased dopamine turnover in the mesolimbic system, reduced preference for an amphetamine cue, and attenuated operant responding for sucrose. The authors also observed that diet-induced obesity with a high-fat diet attenuated mesolimbic dopamine turnover in the nucleus accumbens. These data are consistent with recent hypotheses that the hormonal signals derived from adipose tissue regulate the activity of central nervous system structures involved in reward and motivation, which may have implications for the treatment of obesity and/or addiction.

Figure 1

A) Acquisition of operant responding for sucrose pellets in rats maintained on chow, HFD or pair-fed HFD. B) Progressive ratio responding for sucrose pellets in rats maintained on chow, HFD or pair-fed HFD. * = p<0.05

Figure 2

Progressive ratio responding for sucrose in DR and DIO animals in Experiment 1.2 *=p < 0.05.

Figure 3

A) Mean number of activity counts over 90 minutes in rats maintained on chow or HFD after an acute 1.0 mg/kg dose of D-amphetamine or saline. B) Conditioned place preference score (time in amphetamine-paired compartment/total time spent in amphetamine- and saline-paired compartments) after 6 conditioning sessions with D-amphetamine in male rats fed chow, HFD or pair-fed HFD * = p<0.05.

Figure 4

Dopamine turnover (the ratio of the dopamine metabolite DOPAC to DA) in A) Nucleus accumbens (NAcc) and B) Orbitofrontal cortex (OFC) * = p<0.05