Diet-induced obesity attenuates operant responding for sucrose pellets
Next, we tested the effects of diet induced obesity and exposure to dietary fat on operant responding for sucrose reward. Animals maintained on high-fat under ad libitum feeding conditions prior to training displayed significantly fewer lever presses for sucrose pellets under all schedules of reinforcement [Fs(1,21) > 5.00, p < .05] compared to animals maintained on standard chow (). When tested using a progressive ratio (PR2) schedule of reinforcement, animals maintained on the HF diet exhibited decreased breakpoints relative to animals maintained on the SC diet [t(14) = 3.28, p<0.05]. Similar to the group given ad lib access to HF, PF animals exhibited decreased levels of lever-press responding throughout all schedules of reinforcement [ts(14) > 2.85, p < .05]. These data suggest that high-fat diets are capable of attenuating the reward of sucrose even without the development of obesity.
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
Obesity alone attenuates operant responding for sucrose pellets
Because it is possible that rats maintained on HF diet respond less for sucrose because they find sucrose pellets less rewarding in comparison to the HF maintenance diet, we ran another operant experiment in rats maintained on standard rodent chow. DIO animals maintained on a standard chow diet were significantly heavier (DIO=376.28 ± 5.22; DR=284.09 ± 5.67g) displayed significantly fewer lever presses under all FR schedules of reinforcement relative to DR animals, and when tested under the PR schedule of reinforcement, DIO animals exhibited significantly lower breakpoints than their DR counterparts (p < 0.05, ). A possible interpretation of these data is that obesity by itself is capable of attenuating operant responding independent of diet.
Progressive ratio responding for sucrose in DR and DIO animals in Experiment 1.2 *=p < 0.05.
Exposure to dietary fat attenuates amphetamine conditioned place preference
Rats maintained on a HF diet for twelve weeks were significantly (ps < .05) heavier in comparison to animals maintained on SC diet or the PF control group (HF = 455.18 +/- 13.40 g; SC = 395.34 +/- 7.94 g; PF = 378.45 +/- 9.09 g). Importantly, however, animals maintained on HFD or standard chow did not differ significantly in baseline locomotor activity [F(1,14) = 0.26, p > 0.05] and a 1.0 mg/kg dose of amphetamine significantly increased locomotor activity in both groups compared to saline injection () (main effect of Drug [F(1,14) = 91.47, p < 0.01]; main effect of Time [F(8,112) = 42.40, p < 0.01]; Drug x Time interaction [F(8,112) = 10.38, p < 0.01]). There was no effect of diet on the level of amphetamine-induced locomotion [largest F = 1.26, p = 0.27], which we interpreted as evidence that amphetamine is equally efficacious in both lean and obese animals. Thus, any difference in the capacity of amphetamine to support reward-related learning cannot be accounted for by general physiological actions of amphetamine between these groups.
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- (more ...)
Next, we measured the effect of HF consumption and diet-induced obesity on the acquisition of an amphetamine based conditioned place preference (CPP). indicates that animals in the SC group increased their preference for the compartment in which they received amphetamine, while animals consuming HF did not appear to alter their preference based on experience with amphetamine. An ANOVA using preference for the amphetamine-paired compartment as the dependent variable confirms this observation, yielding a significant interaction between diet condition and pre-training vs. post-training [F(2,21) = 7.10, p<0.01]. One-way repeated measures analysis of each diet condition yielded a significant training effect for the animals consuming standard chow [F(1,7) = 8.25, p<0.05], but not for the ad lib high-fat [F(1,7) = 1.23, p<0.3] or pair-fed high-fat [F(1,7) = 3.12, p< 0.1] groups.
Exposure to dietary fat and obesity decrease DA transmission in the NAcc
Mesolimbic dopamine flux is associated with the ability of animals to respond to cues that predict the delivery of a variety of different types of reward including ingestive (food or liquid), drug, and sex related rewards (Shultz W 1997, 2007). A large body of evidence supports a role for mesolimbic dopamine signaling in food reward paradigms (Bassareo V & Di Chiara G 1999
, Sotak B et. al 2005
), therefore, we sought to determine if a high-fat diet was capable of altering mesolimbic dopamine metabolism. ANOVA revealed a main effect of group on NAcc dopamine turnover [F(1, 18) = 4.163; p<0.05]. Animals given ad libitum
access to the HF diet displayed decreased dopamine turnover in the NAcc relative to SC control animals (p<0.05), as did animals exposed to HF diet without becoming obese (p<0.05, ). There were no differences in dopamine concentration in the NAcc between any of the groups tested. Additionally, there were no differences (ps > .05) in dopamine concentration or turnover in the orbitofrontal cortex (OFC) between any of the three groups (), nor did we observe differences in catecholamine metabolites (DA, 5HT, HVA) in either brain region, suggesting a specific effect of a high-fat diet on dopamine neurochemistry that is restricted to the mesolimbic system.
Dopamine turnover (the ratio of the dopamine metabolite DOPAC to DA) in A) Nucleus accumbens (NAcc) and B) Orbitofrontal cortex (OFC) * = p<0.05