(P09-011-25) A Superstimulus: Glucose Mixed With Saccharin Increases Short-Term Drinking and Dopamine Signaling in the Brain More Than Either Stimulus Alone

Objectives: The combination of the artificial sweetener saccharin (S) together with the caloric sugar glucose (G) is highly appetitive in rodents in 24-hr access tests. Here, we used brief access tests to assess licking for G, S, and G+S to determine whether this phenomenon occurs at earlier time points. To gain insight into the neural mechanisms mediating these effects, we used ex vivo and in vivo strategies to measure neural activity in the gustatory cortex and nucleus accumbens for each stimulus. We hypothesized that mice lick more for G+S than either G or S alone, and that G+S stimulates elevated activity in the nucleus accumbens.

Methods: Sixteen male and female C57BL/6J mice were given 4 mM saccharin and 200 mM glucose alone and in combination for 10 secs in a Davis-rig gustometer. Mice were then presented with either 4 mM saccharin, 200 mM glucose or G+S for 3 minutes with a 200 lick cap followed by immediate sacrifice. Immunohistochemistry identified pERK expression in gustatory cortex, nucleus accumbens core and shell. In a separate cohort, we performed in vivo dopamine recordings via fiber photometry in accumbens core to the same concentrations of sweeteners.

Results: Mice licked more for the G+S in brief access tests (p < 0.05). Mice given G+S on the day of sacrifice had significantly higher pERK immmunopositive cells in the accumbens core than those with access to either G or S alone (p < 0.05). There were no pERK differences among stimuli in gustatory cortex or accumbens shell. Fiber photometry revealed greater dopamine signaling to G+S (p < 0.05) in accumbens core than to either stimulus alone.

Conclusions: Mice licked avidly for G+S in short term tests. G+S stimulated higher pERK signaling in the nucleus accumbens core and greater dopamine signaling than did either stimulus alone.

Funding Sources: This work was supported by the National Institutes of Health (NIDCD and NCCIH).