RESUMEN
The Occidental High- and Low-Saccharin rats (respectively, HiS and LoS lines) were selectively bred for decades to examine mechanisms and correlates of a saccharin intake phenotype. Observed line differences ranged from taste and eating to drug self-administration and defensive behavior, paralleling human research on relationships between gustation, personality, and psychopathology. The original lines were terminated in 2019, and replicate lines (HiS-R and LoS-R) were selectively bred for 5 generations to test for reproducible, rapid selection for the phenotype and its correlates. The line differences chosen for replication included intake of tastants (saccharin, sugars, quinine-adulterated sucrose, sodium chloride, and ethanol) and foods (cheese, peas, Spam, and chocolate) and several noningestive behaviors (deprivation-induced hyperactivity, acoustic startle, and open field behavior). The HiS-R and LoS-R lines diverged on intake of saccharin, disaccharides, quinine-adulterated sucrose, sodium chloride, and complex foods, and open field behavior. Differences from the original lines also were observed. Reasons for and implications of the pattern of replication and lack thereof in 5 generations are discussed.
Asunto(s)
Quinina , Sacarina , Humanos , Ratas , Animales , Sacarina/farmacología , Quinina/farmacología , Cloruro de Sodio , Fenotipo , Sacarosa/farmacología , GustoRESUMEN
The Occidental Low- and High-Saccharin-Consuming rats (respectively, LoS and HiS) have been selectively bred for decades to study the relationship between taste and behaviors in and beyond the ingestive domain. Whether the saccharin phenotype is associated with behavioral periodicities tied to reproductive status is not known. Here we describe for the first time variation across the estrous cycle in chow intake and wheel running by LoS and HiS rats. This study also shed light on why rats, humans, and some other mammals eat less and become more active as fertility increases. Wheel running increases when eating is reduced through restricted chow access, more so in LoS rats than in HiS rats (Dess et al., 2000). If the decrease in food intake from diestrus through estrus causes the increase in running (Eat Less â Run More hypothesis, ELRM), then the running peak should follow the eating nadir and be greater in LoS rats. Bayesian cyclic regression showed that estrous cycles were shorter in LoS rats than in HiS rats; implications are discussed. Contrary to ELRM, the running peak did not follow the eating nadir, and cycle amplitude did not distinguish LoS rats from HiS rats. These results indirectly support the No Time To Eat hypothesis (Fessler, 2003), according to which the periovulatory eating nadir and running peak reflect fitness-enhancing consequences of shifts away from eating and toward mating as fertility increases.
Asunto(s)
Actividad Motora , Gusto , Animales , Teorema de Bayes , Ingestión de Alimentos , Ciclo Estral , Femenino , Fenotipo , RatasRESUMEN
Taste is increasingly recognized as being related to reward, risk, and social processes beyond the ingestive domain. Occidental High (HiS) and Low (LoS) Saccharin Consuming rats have been selectively bred for more than 25 years to study those relationships. The present study examined LoS and HiS rats' sensitivity to a social partner's lineage. The role of gut microbiome transfer between lines was also explored as a possible mediating mechanism. Rats were pair-housed with a rat from either their own line (same-line condition) or the other line (other-line condition); weight gain, saccharin intake, acoustic startle, and open field behavior were measured. Results show for the first time that the lines express different behavioral strategies in a novel open field. In addition, weight gain and open field measures indicate that other-line housing was stressful. Saccharin intake, however, was unaffected by housing condition. A previous finding that the lines possess different gut microbiota was replicated. Although microbial transfer occurred between social partners, no clear evidence was obtained that housing-condition effects on weight gain or behavior were mediated by microbial transfer. Overall, these findings add to the characterization of non-gustatory correlates of a taste phenotype and suggest that rats differing strikingly on the taste phenotype and/or its correlates may be socially incompatible.
Asunto(s)
Microbioma Gastrointestinal , Gusto , Animales , Peso Corporal , Vivienda , Fenotipo , Ratas , SacarinaRESUMEN
Taste signals food quality and reflects energy status and associated processes. Occidental high- and low-saccharin consuming rats (HiS, LoS) have been selectively bred for nearly 60 generations on intake of 0.1% saccharin in a 23-h two-bottle test, as a tool for studying individual differences in taste and its correlates in the domains of feeding, defensive, and social behavior. The saccharin phenotype itself has not been well characterized until now. The present series of parametric studies examined suprathreshold saccharin concentration-intake functions (Experiment 1), saccharin preference threshold (Experiments 2A and 2B), and intra- and inter-sweetener carryforward effects (Experiments 2B, 3A-3D). Results indicate high stability in line differences in behavior toward saccharin and also line-specific mutability of intake of saccharin and certain other sweeteners. Methodological and conceptual implications are discussed.
Asunto(s)
Sacarina/farmacología , Edulcorantes/farmacología , Gusto/efectos de los fármacos , Administración Oral , Animales , Femenino , Masculino , Fenotipo , Ratas , Sacarina/administración & dosificación , Edulcorantes/administración & dosificación , Gusto/genética , Umbral GustativoRESUMEN
A key feature of energy regulation among species that eat discrete meals is meal patterning - meal frequency, size, and duration. Such animals can adjust to internal states and external circumstances with changes in one or more of those meal parameters, with or without altering total food intake. Relatively little is known about individual differences in meal patterning. We previously reported meal patterning differences between rat lines selectively bred for differential saccharin solution intake, lines that also differ in sensitivity to metabolic challenges: Relative to high-saccharin-consuming counterparts (HiS), male low-saccharin-consuming rats (LoS) ate smaller, more frequent meals. Those findings provided evidence of an association between taste and short term satiety. Twenty generations later, we describe systematic replication of the line difference in meal patterns in males and females using two different kinds of reinforcer pellet. The previous study was further extended by examining meal parameters (1) with bi- and multivariate analyses and (2) after acute food restriction and a moderate stressor. Results are discussed within a behavior-systems framework incorporating taste as a marker for behavioral energy regulation.
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Ingestión de Energía/fisiología , Conducta Alimentaria/fisiología , Sacarina/farmacología , Saciedad/fisiología , Edulcorantes/farmacología , Gusto/fisiología , Animales , Femenino , Masculino , RatasRESUMEN
Behavioral responses to sweeteners have been used to study the evolution, mechanisms, and functions of taste. Occidental low and high saccharin consuming rats (respectively, LoS and HiS) have been selectively outbred on the basis of saccharin intake and are a valuable tool for studying variation among individuals in sweetener intake and its correlates. Relative to HiS rats, LoS rats consume smaller amounts of all nutritive and nonnutritive sweeteners tested to date, except aspartame. The lines also differ in intake of the commercial product Splenda; the roles of sucralose and saccharides in the difference are unclear. The present study extends prior work by examining intake of custom mixtures of sucralose, maltodextrin, and sugars and Splenda by LoS and HiS rats (Experiment 1A-1D), stevia and a constituent compound (rebaudioside A; Experiment 2A-2E), and acesulfame potassium tested at several concentrations or with 4 other sweeteners at one concentration each (Experiment 3A-3B). Results indicate that aversive side tastes limit intake of Splenda, stevia, and acesulfame potassium, more so among LoS rats than among HiS rats. In addition, regression analyses involving 5 sweeteners support the idea that both sweetness and bitterness are needed to account for intake of nonnutritive sweeteners, more so among LoS rats. These findings contribute to well developed and emerging literatures on sweetness and domain-general processes related to gustation.
Asunto(s)
Ingestión de Alimentos , Sacarina/administración & dosificación , Stevia/química , Sacarosa/análogos & derivados , Edulcorantes/administración & dosificación , Gusto/efectos de los fármacos , Gusto/genética , Tiazinas/administración & dosificación , Animales , Ratas , Análisis de Regresión , Sacarina/farmacología , Sacarosa/administración & dosificación , Sacarosa/farmacología , Edulcorantes/farmacología , Gusto/fisiología , Tiazinas/farmacologíaRESUMEN
OBJECTIVES: The microbiota-gut-brain axis is increasingly implicated in obesity, anxiety, stress, and other health-related processes. Researchers have proposed that gut microbiota may influence dietary habits, and pathways through the microbiota-gut-brain axis make such a relationship feasible; however, few data bear on the hypothesis. As a first step in the development of a model system, the gut microbiome was examined in rat lines selectively outbred on a taste phenotype with biobehavioral profiles that have diverged with respect to energy regulation, anxiety, and stress. METHODS: Occidental low and high-saccharin-consuming rats were assessed for body mass and chow, water, and saccharin intake; littermate controls had shared cages with rats in the experimental group but were not assessed. Cecum and colon microbial communities were profiled using Illumina 16S rRNA sequencing and multivariate analysis of microbial diversity and composition. RESULTS: The saccharin phenotype was confirmed (low-saccharin-consuming rats, 0.7Δ% [0.9Δ%]; high-saccharin-consuming rats, 28.1Δ% [3.6Δ%]). Regardless of saccharin exposure, gut microbiota differed between lines in terms of overall community similarity and taxa at lower phylogenetic levels. Specifically, 16 genera in three phyla distinguished the lines at a 10% false discovery rate. DISCUSSION: The study demonstrates for the first time that rodent lines created through selective pressure on taste and differing on functionally related correlates host different microbial communities. Whether the microbiota are causally related to the taste phenotype or its correlates remains to be determined. These findings encourage further inquiry on the relationship of the microbiome to taste, dietary habits, emotion, and health.
Asunto(s)
Conducta Animal/fisiología , Microbioma Gastrointestinal/fisiología , Modelos Animales , Fenotipo , Gusto/fisiología , Animales , Masculino , ARN Ribosómico 16S , Ratas , Análisis de Secuencia de ARNRESUMEN
Naïve humans and rats voluntarily consume little ethanol at concentrations above ~6% due to its aversive flavor. Developing procedures that boost intake of ethanol or ethanol-paired flavors facilitates research on neural mechanisms of ethanol-associated behaviors and helps identify variables that modulate ethanol intake outside of the lab. The present study explored the impact on consumption of ethanol and ethanol-paired flavors of nutritionally significant parametric variations: ethanol vehicle (gelatin or solution, with or without polycose); ethanol concentration (4% or 10%); and feeding status (chow deprived or ad lib.) during flavor conditioning and flavor preference testing. Individual differences were modeled by testing rats of lines selectively bred for high (HiS) or low (LoS) saccharin intake. A previously reported preference for ethanol-paired flavors was replicated when ethanol had been drunk during conditioning. However, indifference or aversion to ethanol-paired flavors generally obtained when ethanol had been eaten in gelatin during conditioning, regardless of ethanol concentration, feeding status, or caloric value of the vehicle. Modest sex and line variations occurred. Engaging different behavioral systems when eating gelatin, rather than drinking solution, may account for these findings. Implications for parameter selection in future neurobiological research and for understanding conditions that influence ethanol intake outside of the lab are discussed.
Asunto(s)
Consumo de Bebidas Alcohólicas , Ingestión de Alimentos , Etanol/administración & dosificación , Preferencias Alimentarias , Gelatina , Sacarina , Gusto , Alcoholismo , Animales , Conducta Animal , Privación de Alimentos , Glucanos , Humanos , Masculino , Ratas , Ratas Endogámicas , Factores SexualesRESUMEN
Rats' voluntary ethanol intake varies with dispositional factors and energy status. The joint influences of these were of interest here. We previously reported that rats selectively bred for high voluntary saccharin intake (HiS) consume more ethanol and express more robust conditioning of preference for flavors paired with voluntarily consumed ethanol than do low-saccharin consuming counterparts (LoS). Three new experiments examined the effect of refeeding after an episode of food restriction on ethanol intake and on preference for ethanol-paired flavors in HiS and LoS rats. A 48-h episode of food restriction with wheel running reduced intake of and preference for 4% ethanol (Exp. 1a) and preference for an ethanol-paired flavor (Exp. 1b) during refeeding. Food restriction alone was sufficient to reduce the flavor preference (Exp. 2). Adding fat to the refeeding diet or extending the food restriction period exacerbated the effect (Exp. 3), yielding a frank aversion to ethanol-paired flavors in LoS rats. These studies indicate that rebound from negative energy balance shifts responses to ethanol-associated cues from preference toward aversion. Analyses of bodyweight changes and caloric intake during refeeding support this conclusion and further suggest that lower metabolic efficiency may be a marker for enhanced preference mutability.
Asunto(s)
Consumo de Bebidas Alcohólicas/genética , Consumo de Bebidas Alcohólicas/psicología , Depresores del Sistema Nervioso Central/administración & dosificación , Etanol/administración & dosificación , Privación de Alimentos/fisiología , Preferencias Alimentarias/efectos de los fármacos , Análisis de Varianza , Animales , Animales Recién Nacidos , Dieta Alta en Grasa , Modelos Animales de Enfermedad , Femenino , Hipercinesia/etiología , Masculino , RatasRESUMEN
For social omnivores such as rats and humans, taste is far more than a chemical sense activated by food. By virtue of evolutionary and epigenetic elaboration, taste is associated with negative affect, stress vulnerability, responses to psychoactive substances, pain, and social judgment. A crucial gap in this literature, which spans behavior genetics, affective and social neuroscience, and embodied cognition, concerns links between taste and social behavior in rats. Here we show that rats selectively bred for low saccharin intake are subordinate to high-saccharin-consuming rats when they compete in weight-matched dyads for food, a task used to model depression. Statistical and experimental controls suggest that differential resource utilization within dyads is not an artifact of individual-level processes such as apparatus habituation or ingestive motivation. Tail skin temperature measurements showed that LoS rats display larger hyperthermic responses to social interaction after status is established, evidence linking taste, social stress, autonomic reactivity, and depression-like symptoms. Based on regression using early- and late-competition predictors to predict dyadic disparity in final competition scores, we tentatively suggest that HiS rats emerge as dominant both because of an "early surge" on their part and because LoS acquiesce later. These findings should invigorate the comparative study of individual differences in social status and its relationship to mental and physical health.
Asunto(s)
Conducta Competitiva/efectos de los fármacos , Sacarina/farmacología , Edulcorantes/farmacología , Animales , Conducta Animal/efectos de los fármacos , Conducta Alimentaria/efectos de los fármacos , Fiebre/metabolismo , Masculino , Fenotipo , Ratas , Piel/metabolismo , Gusto/fisiologíaRESUMEN
The "food addiction" concept implies that proneness to drug dependence and to food dependence should covary. The latter was studied in low- (LoS) and high- (HiS) saccharin-consuming rats, who differ in drug self-administration (HiS>LoS) and withdrawal (LoS>HiS). Sugary food intake in the first 1-2 h was higher in HiS than LoS rats. Sugar intake predicted startle during abstinence only among LoS rats. These results may suggest bingeing-proneness in HiS rats and withdrawal-proneness among LoS rats. However, intake escalation and somatic withdrawal did not differ between lines. Further study with selectively bred rats, with attention to definitions and measures, is warranted.
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Conducta Adictiva/genética , Sacarina/administración & dosificación , Animales , Carbohidratos de la Dieta , Etanol , Femenino , Glucosa , Fenotipo , Ratas , Ratas Endogámicas , Reflejo de Sobresalto , AutoadministraciónRESUMEN
Behavioral effects of the same dose of the same drug can vary in degree and direction between and within individuals. The present study examines behavioral base rates, feeding status, and dispositional differences as sources of inter- and intra-individual heterogeneity in drug response. Modulation of the effects of methylphenidate (MPD) on wheel running and acoustic startle by food deprivation was examined in three experiments. Freely fed or food deprived Harlan Sprague-Dawley rats (running study) or rats selectively bred for low (LoS) and high (HiS) saccharin intake (running and startle studies) were given MPD (10 mg/kg) or saline before testing. Overall drug effects and predictors of drug response were assessed. MPD increased running and startle amplitude and disrupted prepulse inhibition; systematic variation among rats of these effects and their modulation by food deprivation was observed. Deprivation-induced running predicted MPD's effect in Harlan SD and LoS rats. Observation of this relationship among commercial rats suggests that acute deprivation sensitivity has utility as a noninvasive marker for drug responses. Its observation in rats selected on a taste phenotype with known correlates points to fruitful avenues of research on stimulant drugs' mechanisms, especially in dopaminergic pathways, and may be relevant to their clinical usage.
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Estimulación Acústica , Estimulantes del Sistema Nervioso Central/farmacología , Privación de Alimentos , Metilfenidato/farmacología , Reflejo de Sobresalto/efectos de los fármacos , Animales , Masculino , Condicionamiento Físico Animal , Ratas , Ratas Sprague-DawleyRESUMEN
Mammals' affinity for sweet tastes exists alongside dramatic variation among species and individuals in responses to sweeteners. The present paper focused on consumption by Occidental High- (HiS) and Low-Saccharin (LoS)-consuming rats in 23-h 2-bottle tests of 2 sweeteners for which few data from rats are available: SC45647 and sucralose. Every HiS and LoS rat preferred SC45647 to water at every concentration, with HiS rats consuming it more avidly. Most HiS rats preferred sucralose to water at one or more concentrations; some HiS rats and most LoS rats avoided sucralose at every concentration. However, both HiS and LoS rats preferred a sucralose-maltodextrin mixture (Splenda) to water; thus, Splenda's "bulking" ingredient maltodextrin transforms highly variable responses to sucralose into a relatively homogeneous preference for the product. Implications for the study of variation in sweet taste are discussed.
Asunto(s)
Preferencias Alimentarias/fisiología , Guanidinas/administración & dosificación , Sacarina/administración & dosificación , Sacarosa/análogos & derivados , Edulcorantes/administración & dosificación , Gusto/fisiología , Animales , Cruzamiento , Ratas , Sacarosa/administración & dosificación , Gusto/genéticaRESUMEN
Exposure to stress can lead to either increased stress vulnerability or enhanced resiliency. Laboratory rats are a key tool in the exploration of basic biobehavioral processes underlying individual differences in the effect of stress on subsequent stressors' impact. The Occidental low (LoS) and high (HiS) saccharin-consuming rats, which differ in emotional reactivity, are useful in this effort. In the present study, footshock affected acoustic startle amplitude 4 h later among LoS but not HiS rats. Surprisingly, shock attenuated startle rather than sensitizing it, a finding not previously reported for male rats exposed to shock. Attenuation was blocked by administering the anxiolytic drug alprazolam prior to stress, implicating anxiety in the effect. Preliminary tests provided no evidence of mediation by adenosine or corticosterone. This novel result encourages further study of the stressor and dispositional variables that modulate the timecourse of effects of stress on startle and identification of its mechanisms.
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Conducta de Ingestión de Líquido/fisiología , Reflejo de Sobresalto/fisiología , Sacarina/administración & dosificación , Estrés Psicológico/fisiopatología , Edulcorantes/administración & dosificación , Gusto/genética , Estimulación Acústica/métodos , Alprazolam/farmacología , Análisis de Varianza , Animales , Ansiolíticos/farmacología , Conducta Animal/efectos de los fármacos , Conducta Animal/fisiología , Cafeína/farmacología , Estimulantes del Sistema Nervioso Central/farmacología , Electrochoque/efectos adversos , Masculino , Ratas , Factores de TiempoRESUMEN
Nearly all mammalian species like sweet-tasting foods and drinks, but there are differences in the degree of 'sweet tooth' both between species and among individuals of the same species. Some individual differences can be explained by genetic variability. Polymorphisms in a sweet taste receptor (Tas1r3) account for a large fraction of the differences in consumption of sweet solutions among inbred mouse strains. We wondered whether mice and rats share the same Tas1r3 alleles, and whether this gene might explain the large difference in saccharin preference among rats. We conducted three experiments to test this. We examined DNA sequence differences in the Tas1r3 gene among rats that differed in their consumption of saccharin in two-bottle choice tests. The animals tested were from an outbred strain (Sprague-Dawley; experiment 1), selectively bred to be high- or low-saccharin consumers (HiS and LoS; experiment 2), or from inbred strains with established differences in saccharin preference (FH/Wjd and ACI; experiment 3). Although there was considerable variation in saccharin preference among the rats there was no variation in the protein-coding regions of the Tas1r3 gene. DNA variants in intronic regions were detected in 1 (of 12) outbred rat with lower-than-average saccharin preference and in the ACI inbred strain, which also has a lower saccharin preference than the FH/Wjd inbred partner strain. Possible effects of these intronic nucleotide variants on Tas1r3 gene expression or the presence of T1R3 protein in taste papillae were evaluated in the ACI and FH/Wjd strains. Based upon the results of these studies, we conclude that polymorphisms in the protein-coding regions of the sweet receptor gene Tas1r3 are uncommon and do not account for individual differences in saccharin preference for these strains of rats. DNA variants in intron 4 and 5 are more common but appear to be innocuous.
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Conducta de Elección/fisiología , Preferencias Alimentarias/fisiología , Polimorfismo Genético , Receptores de Superficie Celular/fisiología , Sacarina/metabolismo , Animales , Variación Genética , Ratas , Ratas Endogámicas , Ratas Sprague-Dawley , Receptores de Superficie Celular/genética , Receptores Acoplados a Proteínas G , Alineación de Secuencia , Especificidad de la Especie , Edulcorantes/metabolismoRESUMEN
Withdrawal severity and voluntary alcohol consumption are inversely related in rats and mice. The present study demonstrated this empirical relation and extended it in two ways. First, the rats were selectively bred for low (LoS) and high (HiS) saccharin intake, a phenotype that correlates positively with ethanol intake and inversely with emotional reactivity. Withdrawal has not yet been studied in these rats. Second, proclivity to consume ethanol was measured as conditioned preference for an ethanol-paired flavor. After 2 weeks of forced exposure to ethanol and a period of abstinence, LoS rats showed elevated acoustic startle; HiS rats did not (Exp. 1). When ethanol- and no-ethanol solutions were available freely during conditioning, both LoS and HiS rats preferred a flavor paired with 4% ethanol, but only HiS rats preferred a flavor paired with 10% ethanol (Exp. 2A); when exposure to the two solutions was controlled, all groups except LoS males preferred flavors paired with 4% or 10% ethanol (Exp. 2B). Thus, as predicted, withdrawal was more severe in the line with less ethanol proclivity (LoS). These results implicate basic associative and affective processes in individual differences in patterns of alcohol use.