Restriction of dietary protein in rats increases progressive-ratio motivation for protein

Low-protein diets can impact food intake and appetite, but it is not known if motivation for food is changed. In the present study, we used an operant behavioral task – the progressive ratio test – to assess whether motivation for different foods was affected when rats were maintained on a protein-restricted diet (REST, 5% protein diet) compared to non-restricted control rats (CON, 18% protein). Rats were tested either with nutritionally-balanced pellets (18.7% protein, Experiment 1) or protein-rich pellets (35% protein, Experiment 2) as reinforcers. Protein restriction increased breakpoint for protein-rich pellets, relative to CON rats, whereas no difference in breakpoint for nutritionally-balanced pellets was observed between groups. When given free access to either nutritionally-balanced pellets or protein-rich pellets, REST and CON rats did not differ in their intake. We also tested whether a previous history of protein restriction might affect present motivation for different types of food by assessing breakpoint of previously REST animals that were subsequently put on standard maintenance chow (protein-repleted rats, REPL, Experiment 2). REPL rats did not show increased breakpoint, relative to their initial encounter with protein-rich pellets while they were protein-restricted. This study demonstrates that restriction of dietary protein induces a selective increased motivation for protein-rich food, a behavior that disappears once rats are not in need of protein

Single prazosin infusion in prelimbic cortex Fosters extinction of amphetamine-induced conditioned place preference

Exposure to drug-associated cues to induce extinction is a useful strategy to contrast cue-induced drug seeking. Norepinephrine (NE) transmission in medial prefrontal cortex has a role in the acquisition and extinction of conditioned place preference induced by amphetamine. We have reported recently that NE in prelimbic cortex delays extinction of amphetamine-induced conditioned place preference (CPP). A potential involvement of α1-adrenergic receptors in the extinction of appetitive conditioned response has been also suggested, although their role in prelimbic cortex has not been yet fully investigated. Here, we investigated the effects of the α1-adrenergic receptor antagonist prazosin infusion in the prelimbic cortex of C57BL/6J mice on expression and extinction of amphetamine-induced CPP. Acute prelimbic prazosin did not affect expression of amphetamine-induced CPP on the day of infusion, while in subsequent days it produced a clear-cut advance of extinction of preference for the compartment previously paired with amphetamine (Conditioned stimulus, CS). Moreover, prazosin-treated mice that had extinguished CS preference showed increased mRNA expression of brain-derived neurotrophic factor (BDNF) and post-synaptic density 95 (PSD-95) in the nucleus accumbens shell or core, respectively, thus suggesting that prelimbic α1-adrenergic receptor blockade triggers neural adaptations in subcortical areas that could contribute to the extinction of cue-induced drug-seeking behavior. These results show that the pharmacological blockade of α1-adrenergic receptors in prelimbic cortex by a single infusion is able to induce extinction of amphetamine-induced CPP long before control (vehicle) animals, an effect depending on contingent exposure to retrieval, since if infused far from or after reactivation it did not affect preference. Moreover, they suggest strongly that the behavioral effects depend on post-treatment neuroplasticity changes in corticolimbic network, triggered by a possible “priming” effect of prazosin, and point to a potential therapeutic power of the antagonist for maladaptive memories

Predictive and motivational factors influencing anticipatory contrast: A comparison of contextual and gustatory predictors in food restricted and free-fed rats

In anticipation of palatable food, rats can learn to restrict consumption of a less rewarding food type resulting in an increased consumption of the preferred food when it is made available. This construct is known as anticipatory negative contrast (ANC) and can help elucidate the processes that underlie binge-like behavior as well as self-control in rodent motivation models. In the current investigation we aimed to shed light on the ability of distinct predictors of a preferred food choice to generate contrast effects and the motivational processes that underlie this behavior. Using a novel set of rewarding solutions, we directly compared contextual and gustatory ANC predictors in both food restricted and free-fed Sprague-Dawley rats. Our results indicate that, despite being food restricted, rats are selective in their eating behavior and show strong contextually-driven ANC similar to free-fed animals. These differences mirrored changes in palatability for the less preferred solution across the different sessions as measured by lick microstructure analysis. In contrast to previous research, predictive cues in both food restricted and free-fed rats were sufficient for ANC to develop although flavor-driven ANC did not relate to a corresponding change in lick patterning. These differences in the lick microstructure between context- and flavor-driven ANC indicate that the motivational processes underlying ANC generated by the two predictor types are distinct. Moreover, an increase in premature port entries to the unavailable sipper – a second measure of ANC – in all groups reveals a direct influence of response competition on ANC development

Protein appetite drives macronutrient-related differences in ventral tegmental area neural activity

Acknowledgements: The authors acknowledge the help and support from the staff of the Division of Biomedical Services, Preclinical Research Facility, University of Leicester, for technical support and the care of experimental animals. The authors would like to thank Vaibhav Konanur for developing the analytical method used to correct fluorescence traces, Leon Lagnado for kindly loaning equipment used in initial photometry experiments, and Andrew MacAskill for useful discussions regarding analysis. This work was funded by the Biotechnology and Biological Sciences Research Council [grant #BB/M007391/1 to J.E.M.], the European Commission [grant #GA 631404 to J.E.M.], The Leverhulme Trust [grant #RPG-2017-417 to J.E.M. and J.A-S.], and Tromsø Research Foundation [grant #19-SGJMcC to J. E. M.).Peer reviewedPublisher PD

Dietary protein restriction alters food-related behaviour and the activity of the mesolimbic pathway

Evolution has provided species with adaptive behavioural mechanisms that guarantee tight dietary protein regulation. However, little is known about how the brain encodes protein need. Here, we elucidate the contribution of the brain reward system in maintaining balanced protein status, examine whether protein need alters food-related motivation and whether protein appetite is innate or learned. We assessed c-fos expressing neurons in the dorsal striatum and nucleus accumbens (NAc) in protein restricted (5% protein diet) and non-restricted (20% protein) rats, after consumption of protein and carbohydrate-containing solutions. After, in two separate cohorts, we expressed the calcium indicator, GCaMP6s, in ventral tegmental area (VTA), or the dopamine sensor, dLight1.2, in the NAc core, and used fibre photometry to measure neural activity or dopamine release during nutrients intake. Additionally, we investigated temporal dynamics of protein consumption when rats first experienced nutrients. Finally, we used a progressive ratio task with protein-rich and nutritionally balanced pellets. Consumption of protein increased the density of c-Fos positive cells in the NAc core and shell of both protein-restricted and non-restricted rats. In photometry experiments, protein consumption, relative to carbohydrate, was associated with elevated VTA activation in protein-restricted rats only. Conversely, carbohydrate consumption was associated with increased dopamine release in the NAc core of nonrestricted rats only. We found that protein was preferred over carbohydrate within the first 5 minutes of exposure to nutrients. Finally, breakpoint for casein pellets was increased in protein-restricted rats, relative to non-restricted controls, whereas there was no difference between groups when nutritionally balanced pellets were used. Altogether, these results indicate an involvement of VTA and NAc in modulating protein appetite. Additionally, protein need elevates the motivation for protein food, and protein appetite does not require previous learning about nutrients to develop. These findings, beyond contributing to the literature, may have positive repercussions for human health.</p