Excessive junk food consumption and the brain reward system in males

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1 Purpose
The brain reward system is a collection of brain structures and neural pathways that are responsible for feelings of pleasure. Food and sexual partners are examples of ‘natural rewards’ that have an unconditioned, inherent pleasurable value. In a functional context, rewards will reinforce individuals to repeat their behavior and turn desire into pursuit and fulfillment. In contrast, a dysfunctional reward system is implicated in disorders such as depression, addiction, and obesity, where the reward system is out of balance.

With food acting on the natural reward system, it is expected that excessive junk food consumption could severely affect this brain circuitry. Overeating of palatable food could overstimulate the reward system and make it dysfunctional/out of balance for future responses. Previous research has focused on the effects of junk food on future food desire and consumption, but the mechanisms of overstimulation of the reward system as a whole, including the responses to other types of rewards, has not been studied before. In our project, we investigate how excessive junk food consumption will overstimulate the reward system, and thereby induce long-lasting changes in brain functioning. We study this by exploring the neural and behavioral changes upon two different rewards: food and sexual behavior. Another running project (FOTS# 19682) studies this in female rats, but since males and female are biologically different, the effects on the brain can also be different. Therefore, this project will focus on the male rats, so that sex comparisons can be made in the future.

The project studies natural reward behavior with novel methods that use genetics to change neurons so that they express special proteins. Now, we can measure the neural activity of specific neurons (fiber photometry) or inhibit the activity of these neurons (chemogenetics). Together, this will reveal the mechanisms underlying natural reward.

2 Distress
The severity category in this proposal is expected to be moderate for most affected animals.

3 Expected benefit
This basic research will contribute to unraveling the complexity of brain reward system. By studying how junk food consumption can overstimulate and disrupt the natural reward system, we generate a better understanding of the functioning of the brain. Deeper understanding of these principles is necessary to explain situations where things go wrong, which ultimately can help finding treatments for reward-related disorders, like addiction and obesity.

4 Number of animals, and what kind
This experiment will need a maximum of 1120 Wistar rats (922 males and 198 females). The project consists of 15 experiments divided into 4 different project-parts.

5 How to adhere to 3R
As we study the neural responses during behavior, the kind of studies cannot be replaced by computer simulations or ex vivo methods. Only in freely moving animals, it is possible to study the neural responses during complex behaviors. Our sophisticated experimental designs with e.g. within-subject approaches and proper power analyses, sufficiently reduce the number of animals needed. Refinement is achieved by using skilled surgeons, appropriate anesthesia/analgesia regimens, group housing and environmental enrichment.