Effects of brain insulin in conditioned place preference using exercise as a reward stimulus

Abstract

Researches suggest that physical activity is effective to prevent or treat stress-related psychiatric disorders such as depression, anxiety, and substance abuse disorders. Both, natural and drugs rewards is processed by the mesolimbic dopamine system; and also this is implicated to rewardrelated behavioral disorders. Studies supports the hypothesis that physical activity act as powerful natural stimulus of the mesolimbic system, using the conditioned place preference (CPP) paradigm with cues associates to voluntary exercise on the running wheel. On the other hand, several studies had reported that insulin can modulated aspects related to memory and learning, which are involved in reward-related behaviors, however, further data are necessary to understand these mechanisms. In addition, an important mediator of insulin/IGF1 (insulinlike growth factor-1) signaling is ERK (extracellular signal–regulated kinases). Evidence supports its implication in learning and memory, and is expressed in the NAcc and activated during exposure to natural and drugs rewards. Our hypothesis is that if insulin signaling can modulate preference to drugs via its effect on dopaminergic transmission in the mesolimbic system, it could similarly modulate preference to the context paired with voluntary exercise. In order to set up the behavior paradigm to study insulin/IGF1 signaling effect in preference for a rewarding stimulus such as exercise, male Wistar rats intraventricular insulin injections treated were used to study the rewarding effects on CPP paired to voluntary wheel running. pERK, IRS2, and IRS1 expression was assessed by immunohistochemical analysis. We found that intraventricular insulin injection showed no significant differences on conditioned place preference using exercise as a reward stimulus. pERK phosphorylation increases in specific brain regions of the insulin injected rats. IRS1 and IRS2 expression displays a different pattern in prefrontal cortex nucleus accumbens and ventral tegmental area. We suggest that the responses of animals in a CPP paradigm can be improved by insulin, due to insulin signaling into the reward areas. Data of immunohistochemical analysis support other studies that reported role of insulin into VTA neurons. Nevertheless, are needed additional research focus on the effects of insulin injections into mesolimbic regions as NAcc or VTA to understand what it is the role of insulin modulating reward-related behaviors.