4.7 Article

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

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NEUROPSYCHOPHARMACOLOGY
卷 44, 期 2, 页码 381-389

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NATURE PUBLISHING GROUP
DOI: 10.1038/s41386-018-0149-y

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资金

  1. Natural Sciences and Engineering Research Council of Canada (NSERC) [203707]
  2. NSERC graduate fellowship
  3. Canadian Institutes of Health Research (CIHR) [MOP-25953]
  4. CIHR Vanier Graduate Fellowship

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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 mu g/mu l SCH-23390) reversed the blockade of conditioned suppression, thereby confirming the causal relationship between ovBNST DA modulation of.-aminobutyric acid transmission and alterations in conditioned suppression following binge-like intake of sucrose.

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