Forsøksdyr: Mapping the brain regulating natural reward


Godkjenningsdato 28.04.2020

Godkjenningsperiode 28.04.2020-27.04.2024

The reward system in the brain is an essential element that is involved in motivation and is responsible for many of our behaviors. Disturbances in this system are related to many disorders like addiction, obesity, and obsessive compulsive behavior, in which the reward system is too active, or anhedonia and sexual dysfunctions in which motivation is lacking.
In this project, we use sexual behavior as a natural incentive-driven behavior to study the motivational system in rats, and investigate which pathways in the brain are involved in natural reward and how they communicate. This will be done with the advanced techniques chemogenetics and fiber photometry. Both methods use genetics to allow neurons to express either designer receptors (chemogenetics) or calcium indicators (fiber photometry). Fiber photometry can measure the neural activity of a specific brain projection within a millisecond scale. Activation of neurons corresponds with increasing levels of intracellular calcium. This calcium then binds to the calcium indicators in the axons, resulting in the emission of a fluorescent signal that can be detected by an implanted fiber. With chemogenetics, on the other hand, specific neural projections can be activated or inhibited by the insertion of a designer drug acting on the designer receptor in the brain. The use of these techniques can reveal the functional roles the specific projections play in natural reward.
The goal of the experiments is to investigate these functional properties of a specific brain regions and their projections during natural reward. In addition, this project is able to study the specific projections without interference of indirect pathways. This project will generate more insights into the role of the communication between brain areas in natural reward measured by sexual motivation and behavior. Disturbances in the reward system are related to many disorders like addiction, obesity, and obsessive compulsive behavior, in which the reward system is too active, or anhedonia and sexual dysfunctions in which motivation is lacking. By investigating how this system works in a normal functioning situation, one could also investigate in future research what could go wrong in patients with these disorders. This could ultimately result in new treatment strategies for disorders linked to reward.
This project will need a maximum of 1258 Wistar rats (1062 males and 196 females), which is carefully calculated with a power analysis. The severity category in this proposal is expected to be moderate. The surgeries are expected to cause no to moderate discomfort for maximum 2 days. We are well trained in the procedures, and all possible measures are taken to reduce the discomfort for the rats.
This kind of experiments can not be replaced by other models. First of all, there are no methods to study brain mechanisms in humans at such a detailed level. Second, computer simulations or in vitro studies are too simplified compared to the reality. Finally, only in living animals it is possible to study these complex behavioral systems.