RESUMEN
Dysregulated appetite is common in autism spectrum disorder (ASD) and it includes excessive interest in tasty foods. Overconsumption of palatable fluids has been found in the valproic acid-induced ASD rat. Though ASD has a strong genetic component, the link between ASD-related genes and appetite for palatable foods remains elusive. We focused on the CNTNAP2 gene whose deletion in mice recapitulates human ASD symptoms. We investigated whether Cntnap2-/- male mice consume greater amounts of palatable 10% sucrose, 0.1% saccharin, and 4.1% intralipid solutions offered in episodic meals either in a no-choice paradigm or a two-bottle choice test. We examined how sucrose intake affects c-Fos immunoreactivity in feeding-related brain areas. Finally, we determined doses at which intraperitoneal oxytocin decreases sucrose intake in mutants. In the single-bottle tests, Cntnap2-/- mice drank more sucrose, saccharin, and intralipid compared to WTs. Given a choice between two tastants, Cntnap2-/- mice had a higher preference for sucrose than intralipid. While the standard 1â mg/kg oxytocin dose reduced sucrose intake in WTs, a low oxytocin dose (0.1â mg/kg) decreased sucrose intake in Cntnap2-/- mice. Sucrose intake induced a more robust c-Fos response in wild-type (WT) than Cntnap2-/- mice in the reward and hypothalamic sites and it increased the percentage of Fos-immunoreactivity oxytocin neurons in WTs, but not in mutants. We conclude that Cntnap2-/- mice overconsume palatable solutions, especially sucrose, beyond levels seen in WTs. This excessive consumption is associated with blunted c-Fos immunoreactivity in feeding-related brain sites, and it can be reversed by low-dose oxytocin.
RESUMEN
A core yet understudied symptom of autism is aberrant eating behaviour, including extremely narrow food preferences. Autistic individuals often refuse to eat despite hunger unless preferred food is given. We hypothesised that, apart from aberrant preference, underfeeding stems from abnormal hunger processing. Utilising an adult male VPA rat, a model of autism, we examined intake of 'bland' chow in animals maintained on this diet continuously, eating this food after fasting and after both food and water deprivation. We assessed body weight in adulthood to determine whether lower feeding led to slower growth. Since food intake is highly regulated by brain processes, we looked into the activation (c-Fos immunoreactivity) of central sites controlling appetite in animals subjected to food deprivation vs. fed ad libitum. Expression of genes involved in food intake in the hypothalamus and brain stem, regions responsible for energy balance, was measured in deprived vs. sated animals. We performed our analyses on VPAs and age-matched healthy controls. We found that VPAs ate less of the 'bland' chow when fed ad libitum and after deprivation than controls did. Their body weight increased more slowly than that of controls when maintained on the 'bland' food. While hungry controls had lower c-Fos IR in key feeding-related areas than their ad libitum-fed counterparts, in hungry VPAs c-Fos was unchanged or elevated compared to the fed ones. The lack of changes in expression of feeding-related genes upon deprivation in VPAs was in contrast to several transcripts affected by fasting in healthy controls. We conclude that hunger processing is dysregulated in the VPA rat.
Asunto(s)
Trastorno Autístico , Ingestión de Alimentos , Animales , Trastorno Autístico/inducido químicamente , Trastorno Autístico/genética , Peso Corporal , Ingestión de Alimentos/genética , Expresión Génica , Masculino , Proteínas Proto-Oncogénicas c-fos/genética , Ratas , Ácido Valproico/efectos adversosRESUMEN
The opioid antagonist naltrexone (NTX) decreases intake of preferred diets in rats at very low doses relative to doses needed to decrease intake of "bland" laboratory chow. In the absence of an opioid agonist, NTX is not discriminable using operant techniques. In the current study, we found that rats given intermittent access to a 25% sucrose solution learned to discriminate between various naltrexone doses and saline. None of the rats given only water learned to discriminate between naltrexone and saline. When access to the sucrose solution was discontinued for 14 days, the rats lost the ability to discriminate between NTX and saline. We also studied the changes of c-Fos IR in selected brain regions in rats treated with saline versus NTX that were drinking water or 25% sucrose. An injection of NTX or saline resulted in a significant drug, diet, and interaction effect in various brain regions associated with feeding behavior, particularly the amygdala, accumbens, and hypothalamic sites. Thus, we found that ingestion of a sucrose solution results in the ability of rats to reliably discriminate naltrexone administration. In addition, sucrose and naltrexone altered c-Fos IR in an interactive fashion in brain regions known to be involved in ingestion behavior.
Asunto(s)
Naltrexona , Receptores Opioides , Animales , Conducta Alimentaria , Naltrexona/farmacología , Antagonistas de Narcóticos/farmacología , Ratas , Sacarosa/farmacologíaRESUMEN
PURPOSE OF REVIEW: In research on autism spectrum disorder (ASD), cognitive, speech- and anxiety-related impairments have been the focus of the majority of studies. One consistently reported ASD symptom that has rarely attracted attention is disordered appetite. The goal of this paper is to assess whether ASD-related dysregulation of food intake impacts consumption of palatable foods, including sugar. RECENT FINDINGS: Aberrant neural processing at the reward system level is at least partially responsible for excessive intake of palatable tastants, including sugar. Impaired oxytocin (OT) signaling likely contributes to the magnitude of this overconsumption. Since intake for reward is generally elevated in individuals with ASD, one strategy to curb sugar overconsumption might utilize presentation of alternative palatable food choices that are more nutritionally adequate than sucrose. Furthermore, OT, which is clinically tested to alleviate other ASD symptoms, might be an effective tool to curb overconsumption of sugar, as well as - likely - of other excessively ingested palatable foods, especially those that have sweet taste.