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Rationale: Although the mesocorticolimbic dopamine (DA) system is the main neurochemical substrate that regulates the addictive and reinforcing effects of ethanol (EtOH), other neurotransmitter systems, such as the acetylcholine (Ach) system, modulate DAergic function in the nucleus accumbens (nAcc). Previously, we reported that intra-nAcc administration of the nicotinic Ach receptor agonist cytisine increased oral EtOH self-administration. GABAB receptors in the nAcc are expressed in DAergic terminals, inhibit the regulation of DA release into the nAcc, and could modulate the effects of cytisine on oral EtOH self-administration. The present study assessed the effects of intra-nAcc administration of the GABAB receptor agonist baclofen (BCF) on the impacts of cytisine on oral EtOH self-administration., Methods: Male Wistar rats were deprived of water for 23.30 h and then trained to press a lever to receive EtOH on an FR3 schedule until a stable response rate of 80 % was achieved. After this training, the rats received an intra-nAcc injection of the nAch receptor agonist cytisine, BCF, and cytisine or 2-hydroxysaclofen, BCF, and cytisine before they were given access to EtOH on an FR3 schedule., Results: Intra-nAcc injections of cytisine increased oral EtOH self-administration; this effect was reduced by BCF, and 2-hydroxysaclofen blocked the effects of BCF., Conclusions: These findings suggest that the reinforcing effects of EtOH are modulated not only by the DA system but also by other neurotransmitter systems involved in regulating DA release from DAergic terminals., Competing Interests: Declaration of competing interest The authors declare no conflicts of interest., (Copyright © 2024 Elsevier Inc. All rights reserved.)

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., (© 2021 Elsevier B.V. All rights reserved.)

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.