Dopamine in the oval bed nucleus of the stria terminalis contributes to compulsive responding for sucrose in rats

Abstract

Binge eating disorder (BED) is characterized by periods of excessive food intake combined with subjective feelings of loss of control. We examined whether sucrose bingeing itself leads to uncontrolled or compulsive responding and whether this effect is magnified following a period of abstinence. We then assessed dopamine (DA) modulation of inhibitory synaptic transmission in the oval bed nucleus of the stria terminalis (ovBNST) as a neural correlate of compulsive responding and whether this behavioral effect could be disrupted by DA blockade in the ovBNST. Over 28 days, male Long-Evans rats (n = 8-16 per group) had access to 10% sucrose and food (12 or 24 h), 0.1% saccharin and food (12 h), or food alone (12 h). Compulsive responding was assessed following 1 or 28 days of sucrose abstinence using a conditioned suppression paradigm. Only rats given 12 h access to sucrose developed binge-like intake, manifested as copious intake within the first hour; compulsive responding was significantly elevated in this group following 28 days of abstinence. In parallel, the effect of DA on ovBNST inhibitory transmission switched from a reduction to a potentiation; the effect, although observable after 1 day, was more pronounced and sustained following 28 days of abstinence. Intra-ovBNST infusions of a DA D1 receptor antagonist (0.8 µg/µl SCH-23390) reversed the blockade of conditioned suppression, thereby confirming the causal relationship between ovBNST DA modulation of γ-aminobutyric acid transmission and alterations in conditioned suppression following binge-like intake of sucrose.

Deletion of mu opioid receptors reduces palatable solution intake in a mouse model of binge eating

“…In sum, rodent models of sucrose bingeing provide valuable insight into the behavioural and biological underpinnings of maladaptive eating. Restricting access to palatable food increases the propensity to binge, leading to alterations in reward processing (Smail-Crevier et al, 2018) as well as neurophysiological changes associated with compulsive responding (Maracle et al, 2018). We now identify a contribution of MORs to binge eating, findings that may translate to clinical treatment (Ziauddeen et al, 2013).…”

The Bed Nucleus of the Stria Terminalis, Homeostatic Satiety, and Compulsions: What Can We Learn From Polydipsia?

“…Functionally, the BNST filters and/or integrates multiple ascending modalities, mapping with adequate resolution, interoceptive information onto motivational systems for adaptive physiological and behavioral outcomes (Jennings et al, 2013; Kim et al, 2013; Lebow and Chen, 2016). Preclinical work compliments studies in humans: we have demonstrated a role for the oval subregion of the BNST (ovBNST) in compulsive behaviors including addiction, compulsive sucrose-seeking, and finally, in SIP (Krawczyk et al, 2013; Gardner Gregory, 2018; Maracle et al, 2019). Accordingly, electrical stimulation of the BNST is reported to suppress SIP in rodents (van Kuyck et al, 2008).…”

A novel GPR55-mediated satiety signal in the oval Bed Nucleus of the Stria Terminalis

“…The ovBNST is ideally organized and connected to regulate diverse motivational states, in part via its synaptic targets [6,[57][58][59][60]. Primarily comprising GABAergic neurons, the BNST can regulate feeding circuits through a monosynaptic GABA projection to the lateral hypothalamus (LH) to suppress glutamatergic neurons and promote feeding [6].…”