Central pramlintide administration potently suppresses operant responding for sucrose and locomotor activity in male rats

Amylin is a feeding-suppressive hormone which acts centrally in the control of energy balance. Some evidence suggests it reduces motivation for food rewards. Pramlintide is a synthetic amylin analog that is used clinically in the treatment of diabetes, and it also reduces feeding and weight gain. However, the mechanisms behind these pramlintide-induced reductions in feeding are unclear. Here we tested the hypothesis that pramlintide would decrease motivation for a palatable food, sucrose pellets. Results show that peripheral (IP) pramlintide had no effect on progressive ratio responding for sucrose pellets. In contrast, intracerebroventricular (ICV) pramlintide reduced active lever pressing, reinforcers earned, and breakpoint for sucrose, even at lower doses subthreshold for effects on 24 h chow intake and body weight change. However, lever pressing behavior was completely abolished for many rats, raising concern for unexpected motor effects. To test whether central pramlintide impacted locomotor activity, we conducted an open field study and found that ICV pramlintide significantly reduced distance traveled at several timepoints, suggesting suppressed locomotor activity. Overall, our results suggest that peripheral pramlintide does not affect motivation for sucrose, and that although central pramlintide does reduce outcomes assessing motivation, this may be confounded by a concurrent reduction in locomotor activity.