Dataset Information

Haloperidol and rimonabant increase delay discounting in rats fed high-fat and standard-chow diets.

ABSTRACT: The dopamine and endocannabinoid neurotransmitter systems have been implicated in delay discounting, a measure of impulsive choice, and obesity. The current study was designed to determine the extent to which haloperidol and rimonabant affected delay discounting in rats fed standard-chow and high-fat diets. Sprague-Dawley rats were allowed to free-feed under a high-fat diet (4.73?kcal/g) or a standard-chow diet (3.0?kcal/g) for 3 months. Then, operant sessions began in which rats (n=9 standard chow; n=10 high-fat) chose between one sucrose pellet delivered immediately versus three sucrose pellets after a series of delays. In another condition, carrot-flavored pellets replaced sucrose pellets. After behavior stabilized, acute injections of rimonabant (0.3-10?mg/kg) and haloperidol (0.003-0.1?mg/kg) were administered intraperitoneally before some choice sessions under both pellet conditions. Haloperidol and rimonabant increased discounting in both groups of rats by decreasing percent choice for the larger reinforcer and area-under-the-curve values. Rats in the high-fat diet condition showed increased sensitivity to haloperidol compared with chow-fed controls; haloperidol increased discounting in both dietary groups in the sucrose condition, but only in the high-fat-fed rats in the carrot-pellet condition. These findings indicate that blocking dopamine-2 and cannabinoid-1 receptors results in increased delay discounting, and that a high-fat diet may alter sensitivity to dopaminergic compounds using the delay-discounting task.

SUBMITTER: Boomhower SR

PROVIDER: S-EPMC4772744 | biostudies-literature | 2014 Dec

REPOSITORIES: biostudies-literature

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Haloperidol and rimonabant increase delay discounting in rats fed high-fat and standard-chow diets.

Boomhower Steven R SR Rasmussen Erin B EB

Behavioural pharmacology 20141201 8

The dopamine and endocannabinoid neurotransmitter systems have been implicated in delay discounting, a measure of impulsive choice, and obesity. The current study was designed to determine the extent to which haloperidol and rimonabant affected delay discounting in rats fed standard-chow and high-fat diets. Sprague-Dawley rats were allowed to free-feed under a high-fat diet (4.73 kcal/g) or a standard-chow diet (3.0 kcal/g) for 3 months. Then, operant sessions began in which rats (n=9 standard c ...[more]

PMID: 25000488

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Project description:Research on the rate at which people discount the value of future rewards has become increasingly prevalent as discount rate has been shown to be associated with many unhealthy patterns of behavior such as drug abuse, gambling, and overeating. fMRI research points to a fronto-parietal-limbic pathway that is active during decisions between smaller amounts of money now and larger amounts available after a delay. Researchers in this area have used different variants of delay discounting tasks and reported various contrasts between choice trials of different types from these tasks. For instance, researchers have compared 1) choices of delayed monetary amounts to choices of the immediate monetary amounts, 2) 'hard' choices made near one's point of indifference to 'easy' choices that require little thought, and 3) trials where an immediate choice is available versus trials where one is unavailable, regardless of actual eventual choice. These differences in procedure and analysis make comparison of results across studies difficult. In the present experiment, we designed a delay discounting task with the intended capability of being able to construct contrasts of all three comparisons listed above while optimizing scanning time to reduce costs and avoid participant fatigue. This was accomplished with an algorithm that customized the choice trials presented to each participant with the goal of equalizing choice trials of each type. We compared this task, which we refer to here as the individualized discounting task (IDT), to two other delay discounting tasks previously reported in the literature (McClure et al., 2004; Amlung et al., 2014) in 18 participants. Results show that the IDT can examine each of the three contrasts mentioned above, while yielding a similar degree of activation as the reference tasks. This suggests that this new task could be used in delay discounting fMRI studies to allow researchers to more easily compare their results to a majority of previous research while minimizing scanning duration.

Project description:BackgroundExcessive fat accumulation of pigs is undesirable, as it severely affects economic returns in the modern pig industry. Studies in humans and mice have examined the role of the gut microbiome in host energy metabolism. Commercial Duroc pigs are often fed formula diets with high energy and protein contents. Whether and how the gut microbiome under this type of diet regulates swine fat accumulation is largely unknown.ResultsIn the present study, we systematically investigated the correlation of gut microbiome with pig lean meat percentage (LMP) in 698 commercial Duroc pigs and found that Prevotella copri was significantly associated with fat accumulation of pigs. Fat pigs had significantly higher abundance of P. copri in the gut. High abundance of P. copri was correlated with increased concentrations of serum metabolites associated with obesity, e.g., lipopolysaccharides, branched chain amino acids, aromatic amino acids, and the metabolites of arachidonic acid. Host intestinal barrier permeability and chronic inflammation response were increased. A gavage experiment using germ-free mice confirmed that the P. copri isolated from experimental pigs was a causal species increasing host fat accumulation and altering serum metabolites. Colon, adipose tissue, and muscle transcriptomes in P. copri-gavaged mice indicated that P. copri colonization activated host chronic inflammatory responses through the TLR4 and mTOR signaling pathways and significantly upregulated the expression of the genes related to lipogenesis and fat accumulation, but attenuated the genes associated with lipolysis, lipid transport, and muscle growth.ConclusionsTaken together, the results proposed that P. copri in the gut microbial communities of pigs fed with commercial formula diets activates host chronic inflammatory responses by the metabolites through the TLR4 and mTOR signaling pathways, and increases host fat deposition significantly. The results provide fundamental knowledge for reducing fat accumulation in pigs through regulating the gut microbial composition. Video Abstract.

Dataset Information

Haloperidol and rimonabant increase delay discounting in rats fed high-fat and standard-chow diets.

Publications

Haloperidol and rimonabant increase delay discounting in rats fed high-fat and standard-chow diets.

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