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.

Fig. 1

Solution and food intake across 28 days for rats given different periods of access to sucrose, saccharin, and food. Data are presented as group means and error bars represent standard error of the mean. a Mean solution intake (ml) as a percentage of body weight (g) during the first hour of each session. b Mean solution intake (ml) as a percentage of body weight (g) across each 24 h session. c Mean food intake (g) as a percent of body weight (g) across each 24 h session. d Mean body weight (g) across sessions. %BW percentage body weight

Fig. 2

Lever pressing data during baseline, retraining, and conditioned suppression testing for groups given different periods of access to sucrose, saccharin, and food. Data are presented as group means and error bars represent 95% CI for each group (a, b), and standard error of the mean (C). a Lever pressing during the final session (baseline) of operant training under a fixed ratio (FR)-5 schedule. b Lever pressing during an operant session (FR-5) following 1 or 28 days of sucrose abstinence. c Conditioned suppression responding following 1 or 28 days of sucrose abstinence. CS ratios were calculated as (total CS-on lever presses/total CS-on + total CS-off lever presses). The vertical line at 0.5 represents consistent responding across CS-on and CS-off phases or a lack of conditioned suppression. *Values significantly lower than this value of 0.5, p < 0.05

Fig. 3

Effect of dopamine (DA) application (5 min) on inhibitory synaptic transmission of ovBNST neurons of rats given different periods of access to sucrose, saccharin, and food. a Schematic illustration of the experimental setting for ovBNST (shaded area in the inset) whole-cell voltage-clamp recordings of GABA_A-inhibitory post-synaptic currents (IPSC). Summary of effects of DA on PPR of GABAA-IPSC in the following groups: 12 h sucrose (b) 1-day abstinence and c 28-day abstinence; 12 h food (d) 1-day abstinence and e 28-day abstinence. Each gray circle represents an individual neuron and black circles/squares are means ± SEM of PPRs at times 0 and 30 min. Representative traces of electrically evoked GABAA-IPSC before (left traces) or after (right traces) bath application DA (1 µM) are shown next to the summary of effects. S1 and S2 represent the maximum GABA_A-IPSC amplitude in response to two electrical stimulations given at 40 Hz to measure changes in paired-pulse ratios (data reported in Results section). Effect of bath application of DA (1 µM, black horizontal bar) on the change in amplitude of electrically evoked GABAA-IPSC amplitude as a function of time following (f) 1-day abstinence or g 28-day abstinence. Data are presented as mean of 30 s bins (5 events/bin) and error bars represent standard error of the mean

Fig. 4

Relationship between sucrose consumption and behavioral and electrophysiological measures for animals given intermittent (12 h) access to sucrose over 28 days. The relationship between amount of sucrose consumed during the first hour of access over the last four consumption sessions and a suppression of responding in the conditioned suppression task or b magnitude of change in GABA_A IPSCs

Fig. 5

Effects of intra-ovBNST DA D1 receptor blockade on conditioned suppression responding. a Drawing showing correct intracranial cannulae placements for rats receiving 0.8 µg/µl SCH-23990 infusions. For clarity, each bilateral infusion is represented unilaterally (total n = 32) and infusions in the 12 h sucrose consumption group are identified with X (n = 8). b Conditioned suppression (CS) ratios and c latency to lever press during CS testing for rats in different access groups following ovBNST infusions of SCH-23990 or saline. CS ratios were calculated as (total CS-on lever presses/total CS-on + total CS-off lever presses). The vertical line at 0.5 represents consistent responding across CS-on and CS-off phases or a lack of conditioned suppression. *Values significantly lower than this value of 0.5, p < 0.05