Corrigendum: Intra-accumbens raclopride administration prevents behavioral changes induced by intermittent access to sucrose solution.

[This corrects the article DOI: 10.3389/fnins.2018.00074.].

CB1/5-HT/GABA interactions and food intake regulation.

Despite historically the serotonergic, GABAergic, and cannabinoid systems have been shown to play a crucial role in the central regulation of eating behavior, interest in the study of the interactions of these neurotransmission systems has only now been investigated. Current evidence suggests that serotonin may influence normal and pathological eating behavior in significantly more complex ways than was initially thought. This knowledge has opened the possibility of exploring the potential clinical utility of new therapeutic strategies more effective and safer than the current approaches to treat pathological eating behavior. Furthermore, the nature and complexity of the interactions between these neurotransmitter systems have provided a better understanding of the pathophysiological mechanisms not only of eating behavior and eating disorders but also of some of the comorbidities associated with modulation of cortical circuits, which are involved in high order cognitive processes. Accordingly, in the present chapter, the clinical and experimental findings of the interactions between serotonin, GABA, and cannabinoids are synthesized, emphasizing the pharmacological, neurophysiological, and neuroanatomical aspects that could potentially improve the current therapeutic approaches against pathological eating behavior.

Intra-accumbens Raclopride Administration Prevents Behavioral Changes Induced by Intermittent Access to Sucrose Solution.

Overeating is one of the most relevant clinical features in Binge Eating Disorder and in some obesity patients. According to several studies, alterations in the mesolimbic dopaminergic transmission produced by non-homeostatic feeding behavior may be associated with changes in the reward system similar to those produced by drugs of abuse. Although it is known that binge-eating is related with changes in dopaminergic transmission mediated by D2 receptors in the nucleus accumbens shell (NAcS), it has not been determined whether these receptors may be a potential target for the treatment of eating pathology with binge-eating. Accordingly, the aim of the present study was to evaluate whether sugar binging induced by intermittent access to a sucrose solution produced changes in the structure of feeding behavior and whether blocking D2 receptors prevented these changes. We used the intermittent access model to a 10% sucrose solution (2 h/day for 4 weeks) to induce sugar binging in Sprague Dawley female rats. Experimental subjects consumed in a 2-h period more than 50% of the caloric intake consumed by the subjects with ad-lib access to the sweetened solution without any increase in body weight or fat accumulation. Furthermore, we evaluated whether sugar binging was associated to the estrous cycle and we did not find differences in caloric intake (estrous vs. diestrus). Subsequently, we characterized the structure of feeding behavior (microstructural analysis) and the motivation for palatable food (breakpoints) of the subjects with sugar binging and found that feeding episodes had short latencies, high frequencies, as well as short durations and inter-episode intervals. The intermittent access model did not increase breakpoints, as occurred in subjects with ad-lib access to the sucrose. Finally, we evaluated the effects of D2 receptor blockade in the NAcS, and found that raclopride (18 nM) prevented the observed changes in the frequency and duration of episodes induced by intermittent access to the sucrose solution. Our results suggest that alterations in behavioral patterns associated with binge-eating behavior depend in part on the dopaminergic transmission in the NAcS and that the antagonism of D2 receptors may be a therapeutic tool for feeding pathology with binge-eating.

Effects of CB1 cannabinoid receptor activation in the nucleus accumbens shell on feeding behavior / Efectos de la activación del receptor cannabinoide CB1 en el núcleo accumbens shell sobre la conducta alimentaria / Efeitos da ativação do receptor cannabinóide CB1 no núcleo accumbens shell sobre a conduta alimentar

Obesity and its related pathologies are well- known health hazards. Although obesity and overweight have multifactorial causes, overeating is common in both of these conditions. According to animal models, endocannabinoids and their receptors in the brain play a key role in the genesis and development of obesity. It has been proposed that the cannabinoid receptors CB1 (RCB1) expressed in the nucleus accumbens shell (NAC) are involved in the increase of the hedonic properties of food. To test this hypothesis, this study aimed to assess the effects of activating the NACs RCB1 on standard food intake during the light phase of the light-dark cycle. The effects of activating the RCB1 with CP 55,940 and WIN 55-212-2 (0.125, 0.25 and 0.5 nmol) in the NACS on feeding behavior and the behavioral satiety sequence of rats were assessed. It was found that both agonists increased food intake and delayed expression of satiety during the light phase. These results suggest that cannabinoid agonists encourage food intake when motivation is low and palatability is normal.

La obesidad y sus patologías relacionadas son riesgos de salud muy conocidos. Aunque la obesidad y el sobrepeso tienen causas multifactoriales, la sobreingesta de alimento es frecuente en estas condiciones. De acuerdo con modelos animales, los endocanabinoides y sus receptores en el cerebro juegan un papel clave en la génesis y desarrollo de la obesidad. Se ha propuesto que los receptores a canabinoides CB1 (RCB1) expresados en el núcleo accumbens shell (NAcS) están involucrados en el incremento de las propiedades hedónicas del alimento. Para probar esta hipótesis, este estudio tuvo como objetivo evaluar los efectos de la activación de los RCB1 en el NAcS sobre la ingesta de alimento estándar durante la fase de luz del ciclo luz-oscuridad. Se evaluaron los efectos de la activación de los RCB1 con WIN 55-212-2 y CP 55,940 (0.125, 0.25, y 0.5 nmol) en el NAcS sobre la conducta alimentaria y la secuencia de saciedad conductual en ratas. Se encontró que ambos agonistas aumentaron la ingesta de alimento y demoraron la expresión de la saciedad durante la fase de luz. Lo anterior sugiere que los agonistas canabinoides estimulan el consumo de alimento cuando la motivación por el mismo es baja y la palatabilidad es normal.

A obesidade e suas patologias relacionadas são riscos de saúde muito conhecidos. Ainda que a obesidade e o sobrepeso possuam causas multifatoriais, a sobre ingestão de alimento é frequente nestas condições. De acordo com modelos animais, os endocanabinóides e seus receptores no cérebro jogam um papel chave na gênese e desenvolvimento da obesidade. Foi proposto que os receptores a canabinóides CB1 (RCB1) expressos no núcleo accumbens shell (NAcS) estão envolvidos no aumento das propriedades hedônicas do alimento. Para testar esta hipótese, este estudo teve como objetivo avaliar os efeitos da ativação dos RCB1 nos NAcS sobre a ingestão de alimento padrão durante a fase de luz do ciclo luz-escuridão. Avaliaram-se os efeitos da ativação dos RCB1 com WIN 55-212-2 e CP 55,940 (0.125, 0.25, e 0.5 nmol) no NAcS sobre a conduta alimentar e a sequência de saciedade condutual em ratos. Encontrou-se que ambos agonistas aumentaram a ingestão de alimento e demoraram a expressão da saciedade durante a fase de luz. Isso sugere que os agonistas canabinóides estimulam o consumo de alimento quando a motivação pelo mesmo é baixa e a palatabilidade é normal.