The effect of the demyelinating agent cuprizone on binge-like eating of sweetened palatable food in female and male C57BL/6 substrains.
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ABSTRACT:
SUBMITTER: Babbs RK
PROVIDER: S-EPMC7206526 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Binge eating is the core, maladaptive eating behavior that cuts across several major types of eating disorders. Binge eating is associated with a significant loss of control over palatable food (PF) intake, and deficits in behavioral control mechanisms, subserved by the prefrontal cortex (PFC), may underlie binge eating. Few studies, to date, have examined whether the PFC is directly involved in the expression of binge eating. As such, the present study investigated the functional role of the medial PFC (mPFC) in PF consumption, using an individual differences rat model of binge eating proneness. Here, we tested the hypothesis that binge eating proneness (i.e., high levels of PF consumption) is associated with reduced mPFC-mediated behavioral control over PF intake. In experiment 1, we quantified PF-induced Fos expression in both excitatory and inhibitory neurons within the mPFC in binge eating prone (BEP) and binge eating resistant (BER) female rats. In experiment 2, we pharmacologically inactivated the mPFC of BEP and BER female rats, just prior to PF exposure, and subsequently quantified PF intake and scores of feeding behavior. While most Fos-expressing neurons of the mPFC in both BEPs and BERs were of the excitatory phenotype, fewer excitatory neurons were engaged by PF in BEPs than in BERs. Moreover, pharmacological inactivation of the mPFC led to a significant increase in PF intake in both BEPs and BERs, but the rise in PF consumption was stronger in BEPs than in BERs. Thus, these data suggest that lower, PF-induced excitatory tone in the mPFC of BEP rats may lead to a weaker, mPFC-mediated behavioral "brake" over excessive PF intake.
| S-EPMC6834655 | biostudies-literature
Project description:Cyclic AMP (cAMP)-dependent signaling is highly implicated in the pathophysiology of alcohol use disorder (AUD), with evidence supporting the efficacy of inhibiting the cAMP hydrolyzing enzyme phosphodiesterase 4 (PDE4) as a therapeutic strategy for drinking reduction. Off-target emetic effects associated with non-selective PDE4 inhibitors has prompted the development of selective PDE4 isozyme inhibitors for treating neuropsychiatric conditions. Herein, we examined the effect of a selective PDE4B inhibitor A33 (0-1.0 mg/kg) on alcohol drinking in both female and male mice from two genetically distinct C57BL/6 substrains. Under two different binge-drinking procedures, A33 pretreatment reduced alcohol intake in male and female mice of both substrains. In both drinking studies, there was no evidence for carry-over effects the next day; however, we did observe some sign of tolerance to A33's effect on alcohol intake upon repeated, intermittent, treatment (5 injections of 1.0 mg/kg, every other day). Pretreatment with 1.0 mg/kg of A33 augmented sucrose intake by C57BL/6NJ, but not C57BL/6J, mice. In mice with a prior history of A33 pretreatment during alcohol-drinking, A33 (1.0 mg/kg) did not alter spontaneous locomotor activity or basal motor coordination, nor did it alter alcohol's effects on motor activity, coordination or sedation. In a distinct cohort of alcohol-naïve mice, acute pretreatment with 1.0 mg/kg of A33 did not alter motor performance on a rotarod and reduced sensitivity to the acute intoxicating effects of alcohol. These data provide the first evidence that selective PDE4B inhibition is an effective strategy for reducing excessive alcohol intake in murine models of binge drinking, with minimal off-target effects. Despite reducing sensitivity to acute alcohol intoxication, PDE4B inhibition reduces binge alcohol drinking, without influencing behavioral sensitivity to alcohol in alcohol-experienced mice. Furthermore, A33 is equally effective in males and females and exerts a quantitatively similar reduction in alcohol intake in mice with a genetic predisposition for high versus moderate alcohol preference. Such findings further support the safety and potential clinical utility of targeting PDE4 for treating AUD.
| S-EPMC8196757 | biostudies-literature
Project description:Binge eating disorder (BED) is the most frequent eating disorder, for which current pharmacotherapies show poor response rates and safety concerns, thus highlighting the need for novel treatment options. The lipid-derived messenger oleoylethanolamide (OEA) acts as a satiety signal inhibiting food intake through the involvement of central noradrenergic and oxytocinergic neurons. We investigated the anti-binge effects of OEA in a rat model of binge-like eating, in which, after cycles of intermittent food restrictions/refeeding and palatable food consumptions, female rats show a binge-like intake of palatable food, following a 15-min exposure to their sight and smell ("frustration stress"). Systemically administered OEA dose-dependently (2.5, 5, and 10 mg kg-1) prevented binge-like eating. This behavioral effect was associated with a decreased activation (measured by mapping the expression of c-fos, an early gene widely used as a marker of cellular activation) of brain areas responding to stress (such as the nucleus accumbens and amygdala) and to a stimulation of areas involved in the control of food intake, such as the VTA and the PVN. These effects were paralleled, also, to the modulation of monoamine transmission in key brain areas involved in both homeostatic and hedonic control of eating. In particular, a decreased dopaminergic response to stress was observed by measuring dopamine extracellular concentrations in microdialysates from the nucleus accumbens shell, whereas an increased serotonergic and noradrenergic tone was detected in tissue homogenates of selected brain areas. Finally, a decrease in corticotropin-releasing factor (CRF) mRNA levels was induced by OEA in the central amygdala, while an increase in oxytocin mRNA levels was induced in the PVN. The restoration of a normal oxytocin receptor density in the striatum paralleled the oxytocinergic stimulation produced by OEA. In conclusion, we provide evidence suggesting that OEA might represent a novel potential pharmacological target for the treatment of binge-like eating behavior.
| S-EPMC7609309 | biostudies-literature
Project description:The inbred mouse strain C57BL/6 has been widely used as a background strain for spontaneous and induced mutations. Developed in the 1930s, the C57BL/6 strain diverged into two major groups in the 1950s, namely, C57BL/6J and C57BL/6N, and more than 20 substrains have been established from them worldwide. We previously reported genetic differences among C57BL/6 substrains in 2009 and 2015. Since then, dozens of reports have been published on phenotypic differences in behavioral, neurological, cardiovascular, and metabolic traits. Substrains need to be chosen according to the purpose of the study because phenotypic differences might affect the experimental results. In this paper, we review recent reports of phenotypic and genetic differences among C57BL/6 substrains, focus our attention on the proper use of C57BL/6 and other inbred strains in the era of genome editing, and provide the life science research community wider knowledge about this subject.
| S-EPMC8150240 | biostudies-literature
Project description:OBJECTIVE:The present study evaluated the effect of systemic injection of the CRF1 receptor antagonist R121919, the corticosterone synthesis inhibitor metyrapone and central amygdala (CeA) injections of the nonselective CRF antagonist D-Phe-CRF(12-41) in rats in which binge eating was evoked by stress and cycles of food restriction. METHOD:Female rats were subjected or not to repeated cycles of regular chow food restriction/ad libitum feeding during which they were also given limited access (2 h) to palatable food. On the test day, rats were either exposed or not to the sight of the palatable food for 15 min without allowing access, before assessing food consumption. RESULTS:Systemic injections of R121919, but not of the metyrapone, blocked binge-like eating behavior. Restricted and stressed rats showed up-regulation of crh1 receptor mRNA signal in the bed nucleus of the stria terminalis and CeA but not in basolateral amygdala (BLA) or in the paraventricular nucleus. Injection D-Phe-CRF(12-41) in CeA but not in the BLA-blocked binge-like eating behavior. DISCUSSION:These findings demonstrate that extra-hypothalamic CRF1 receptors, rather than those involved in endocrine functions, are involved in binge eating and the crucial role of CRF receptors in CeA. CRF1 receptor antagonism may represent a novel pharmacological treatment for binge-related eating disorders.
| S-EPMC5772704 | biostudies-literature
Project description:Binge eating disorder (BED) is characterized by regular binge eating episodes during which individuals ingest comparably large amounts of food and experience loss of control over their eating behaviour. The worldwide prevalence of BED for the years 2018-2020 is estimated to be 0.6-1.8% in adult women and 0.3-0.7% in adult men. BED is commonly associated with obesity and with somatic and mental health comorbidities. People with BED experience considerable burden and impairments in quality of life, and, at the same time, BED often goes undetected and untreated. The aetiology of BED is complex, including genetic and environmental factors as well as neuroendocrinological and neurobiological contributions. Neurobiological findings highlight impairments in reward processing, inhibitory control and emotion regulation in people with BED, and these neurobiological domains are targets for emerging treatment approaches. Psychotherapy is the first-line treatment for BED. Recognition and research on BED has increased since its inclusion into DSM-5; however, continuing efforts are needed to understand underlying mechanisms of BED and to improve prevention and treatment outcomes for this disorder. These efforts should also include screening, identification and implementation of evidence-based interventions in routine clinical practice settings such as primary care and mental health outpatient clinics.
| S-EPMC9793802 | biostudies-literature
Project description:ObjectiveAlthough several effective behavioral treatments for binge-eating disorder (BED) exist, there are racial disparities in treatment access, with African-Americans and/or Black individuals having some of the lowest rates of access to care. Little is known about the experience and treatment of binge eating (BE) and BED among Black women.MethodThis systematic review, conducted according to PRISMA guidelines, synthesizes information related to BE and BED in Black women.ResultsA total of N = 38 studies met our eligibility criteria. We did not identify any systematic risk of bias across studies. The majority of included studies used cross-sectional survey methodology, and relied on interview (EDE) and self-report measures (particularly the Binge Eating Scale, BES) for the assessment of BE. Outcomes were inconsistently measured across trials, and there are limited data on the results of evidence-based treatments for BE/BED in Black women.DiscussionAlthough Black women have similar or higher rates of BE than White women, most research on BE and BED has focused on White women, with Black individuals underrepresented in clinical trials. Future research should examine evidence-based treatments to prevent and treat BED in this population.ObjetivoAunque existen varios tratamientos conductuales que son efectivos para el Trastorno de Atracones (BED, por sus siglas en inglés), existen disparidades raciales en el acceso a tratamiento, con individuos Afroamericanos y/o personas de color teniendo algunas de las tasas más bajas de acceso al cuidado de la salud. Se sabe muy poco acerca de la experiencia y tratamiento del comer en atracones (BE, por sus siglas en inglés) y BED entre mujeres afroamericanas y/o de color. MÉTODO: Esta revisión sistemática, realizada bajo lineamientos de las guías PRISMA, sintetiza información relacionada con BE y BED en mujeres afroamericanas y/o de color.ResultadosUn total de N = 38 estudios cumplieron con nuestros criterios de elegibilidad. No identificamos ningún riesgo sistemático de sesgo entre los estudios. La mayoría de los estudios incluidos utilizaron una metodología de encuesta transversal y se basaron en la entrevista (EDE) y las medidas de autoinforme (en particular, la Binge Eating Scale, BES) para la evaluación de BE. Los resultados se midieron de manera inconsistente entre los ensayos, y hay datos limitados sobre los resultados de los tratamientos basados en la evidencia para BE/BED en mujeres afroamericanas y/o de color. DISCUSIÓN: Aunque las mujeres afroamericanas y/o de color tienen tasas similares o más altas de BE que las mujeres blancas, la mayoría de las investigaciones sobre BE y BED se han centrado en las mujeres blancas, con individuos afroamericanos y/o de color subrepresentados en ensayos clínicos. La investigación futura debería examinar los tratamientos basados en la evidencia para prevenir y tratar el BED en esta población.
| S-EPMC8010989 | biostudies-literature
Project description:Binge eating (BE) is a heritable symptom of eating disorders associated with anxiety, depression, malnutrition, and obesity. Genetic analysis of BE could facilitate therapeutic discovery. We used an intermittent, limited access BE paradigm involving sweetened palatable food (PF) to examine genetic differences in BE, conditioned food reward, and compulsive-like eating between C57BL/6J (B6J) and DBA/2J (D2J) inbred mouse strains. D2J mice showed a robust escalation in intake and conditioned place preference for the PF-paired side. D2J mice also showed a unique style of compulsive-like eating in the light/dark conflict test where they rapidly hoarded and consumed PF in the preferred unlit environment. BE and compulsive-like eating exhibited narrow-sense heritability estimates between 56 and 73%. To gain insight into the genetic basis, we phenotyped and genotyped a small cohort of 133 B6J × D2J-F2 mice at the peak location of three quantitative trait loci (QTL) previously identified in F2 mice for sweet taste (chromosome 4: 156?Mb), bitter taste (chromosome 6: 133?Mb) and behavioral sensitivity to drugs of abuse (chromosome 11: 50?Mb). The D2J allele on chromosome 6 was associated with greater PF intake on training days and greater compulsive-like PF intake, but only in males, suggesting that decreased bitter taste may increase BE in males. The D2J allele on chromosome 11 was associated with an increase in final PF intake and slope of escalation across days. Future studies employing larger crosses and genetic reference panels comprising B6J and D2J alleles will identify causal genes and neurobiological mechanisms.
| S-EPMC6333425 | biostudies-literature
Project description:This report examined baseline affective response to binge eating as a predictor of binge-eating disorder (BED) treatment outcome. Baseline affective response was defined as: (1) each individual's average net change (i.e., area under the curve [AUC]) of positive affect (PA) or negative affect (NA) before and after binge-eating episodes and (2) post-binge eating slope of PA or NA across seven-days of ecological momentary assessment (EMA). Adults with BED completed Integrative Cognitive-Affective Therapy (ICAT-BED) or cognitive behavioral therapy guided self-help (CBTgsh). Individuals with greater net increases in PA (AUC) following binge eating at baseline exhibited better treatment response in ICAT-BED at end-of-treatment and follow-up. NA affective response was only significant at end-of-treatment; individuals with less rapid post-binge improvements in NA (slope) did better in ICAT-BED, while individuals with lower net improvements in NA (AUC) did better in CBTgsh. Affective response to binge eating may be a marker of BED treatment response.
| S-EPMC8579466 | biostudies-literature
Project description:Drug liking vs. drug disliking is a subjective motivational measure in humans that assesses the addiction liability of drugs. Variation in this trait is hypothesized to influence vulnerability vs. resilience toward substance abuse disorders and likely contains a genetic component. In rodents and humans, conditioned place preference (CPP)/aversion (CPA) is a Pavlovian conditioning paradigm whereby a learned preference for the drug-paired environment is used to infer drug liking whereas a learned avoidance or aversion is used to infer drug disliking. C57BL/6 inbred mouse substrains are nearly genetically identical, yet demonstrate robust differences in addiction-relevant behaviors, including locomotor sensitization to cocaine and consumption of ethanol. Here, we tested the hypothesis that B6 substrains would demonstrate differences in the rewarding properties of the mu opioid receptor agonist oxycodone (5 mg/kg, i.p.) and the aversive properties of the opioid receptor antagonist naloxone (4 mg/kg, i.p.). Both substrains showed similar degrees of oxycodone-induced CPP; however, there was a three-fold enhancement of naloxone-induced CPA in agonist-naïve C57BL/6J relative to C57Bl/6NJ mice. Exploratory factor analysis of CPP and CPA identified unique factors that explain variance in behavioral expression of reward vs. aversion. "Conditioned Opioid-Like Behavior" was a reward-based factor whereby drug-free locomotor variables resembling opioid treatment co-varied with the degree of CPP. "Avoidance and Freezing" was an aversion-based factor, whereby the increase in the number of freezing bouts co-varied with the degree of aversion. These results provide new insight into the behavioral architecture of the motivational properties of opioids. Future studies will use quantitative trait locus mapping in B6 substrains to identify novel genetic factors that contribute to the marked strain difference in NAL-CPA.
| S-EPMC4290583 | biostudies-literature