Role of Neurotensin Receptor‐1 Expression in Dopamine Neurons for Feeding, Locomotor and Anxiety Behaviors

Abstract

The dopamine (DA) system is essential for motivated feeding and locomotion, but disruption of this system is implicated in the development of obesity and low body weight, namely anorexia nervosa. All DA neurons transiently express the neurotensin receptor‐1 (NtsR1) during development, suggesting that this receptor may contribute to the establishment and/or function of the DA system. Thus, we hypothesized that lacking NtsR1 expression in DA neurons impairs the function of the DA system and DA‐dependent feeding, locomotor activity, and anxiety behaviors. To test this, we crossed DATCre/+ and NtsR1flox/floxmice to generate mice with intact NtsR1 (Controls ‐ DAT+/+; NtsR1flox/flox) or mice in which NtsR1 was selectively deleted from DA neurons (DATCre/+; NtsR1flox/floxmice). We then assessed mice of each genotype and sex for feeding and physical activity, DA‐dependent behaviors and body weight. Feeding and body weight were similar in Control mice and those lacking NtsR1 from DA neurons. However, mice lacking NtsR1 in DA neurons exhibited more locomotor activity than Control mice. This altered locomotor activity was not due to altered stress or anxiety like behaviors, nor differences in dopamine‐ dependent behaviors, as these were similar between Control and NtsR1‐deficient mice. Thus, in contrast to our hypothesis, developmental deletion of NtsR1 deletion from dopamine neurons does not disrupt regulation of body weight or behavior, and is likely not a pathogenetic contributor to disordered body weight.