Why Study Invertabrates? Fly Mice are Good Model Organisms for Addiction Research The Reward Pathway is Fundamental

Food, nurturing and social interaction are essential for the survival of not only humans, but also of animals. These things were responsible for shaping the first reward pathway in an ancestral animal that lived millions of years ago, soon after the first brain tissue appeared.

Once it appeared, the reward pathway was passed down from generation to generation through a process called natural selection. Because the reward pathway increased animals' chances of reproducing, it was "selected" for, meaning it was genetically transmitted from one generation to the next. Over time the reward pathway remained a central part of the brain, even as the rest of the brain became more complex.

Because animals and humans share the reward pathway and most of the genes that govern it, animals are also susceptible to drug addiction. This makes animals a convenient tool for researchers who study addiction.

Limbic system (including the reward pathway). Responsible for instincts, feeding, fighting, fleeing and sexual behavior.

Cerebral cortex. Oversees and controls more primitive regions of the brain. Allows more sensation and control of complex aspects of the environment.

Cerebellum and brain stem. Responsible for muscle control, balance and autonomic functions, such as breathing and heartbeat.

The structures near the base (blue) and center (pink) of the human brain are evolutionarily very old. We share many of these structures with fish, amphibians and reptiles.

Chimpanzee

Chimpanzee Pan troglodytes
20,000-25,000 genes (same as human)

There are just 50 human genes with no known homolog in chimps. Of the protein-coding genes in the human and chimp genomes, one-third have identical sequences.

Mouse

Mouse Mus musculus
20,000-25,000 genes (same as human)

The average mouse gene is about 85% similar to its human homolog.

Fish

Zebrafish Danio rerio
25,000 genes

Scientists routinely transfer human genes into zebrafish and study their functions.

Fruitfly Drosophila Melanogaster
13,600 genes

Approximately 60% of known human disease genes have a counterpart in the fruit fly.

Worm

Roundworm Caenorhabditis elegans
19,100 genes

Earliest organism with a central nervous system. Shares about 21% of its genes with humans.

The genomes of many organisms commonly used in research have been sequenced and can be compared to the human genome.

Animal Models and Gene Discovery

Animals are particularly valuable as a research tool because they allow scientists to conduct experiments that they could never perform on humans. Many animals, especially mice, are leading the way in developing our understanding of the complex disease of addiction.

When researchers discover a gene in a model organism that plays a role in addiction, they can then identify the counterpart gene in humans by using a computer to compare DNA sequences. They can then study the human gene.

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When humans have a gene in common with another organism, scientists call the counterpart gene a 'homolog' or a 'homologous gene.'

Humans and vertebrate animals share the reward pathway and most of the genes that control it. But even organisms that lack a complex brain such as the fruit fly and roundworm share many of the components that make up the reward pathway. They have the same neurotransmitters, receptors and signaling mechanisms as we do. So scientists commonly study a variety of animals to learn about different aspects of human biology, including the reward pathway.

Of Mice and Men: How Similar Are We?

Mice and humans are similar genetically, so what is it that makes them so different? A human gene may differ slightly in its DNA sequence, for example. Or genes may also be active at different times or in different tissues throughout the development and life of the organism. Where and when a gene's protein product is made can sometimes result in dramatic differences between organisms, contributing to their overall appearance and unique abilities.

Human Brain

Rat Brain

Brain Diagram

Rodents share more than just the reward pathway with humans. The entire set-up of the brain is nearly identical. Both use the same neurotransmitters and receptors, the same proteins for synaptic vesicle release and recycling, and similar signaling mechanisms.

Mouse Models for Addiction?

Decades ago, researchers first tested laboratory strains of rats and mice for specific addiction traits, such as high preference for certain drugs or alcohol. Since individuals within a laboratory strain are virtually identical, they all have the same addiction profile. But researchers discovered that individuals from different strains had vastly different addiction profiles. This was one of the earliest clues that addiction has a genetic component.

Researchers also learned that by selectively breeding rats or mice with certain addiction traits they could generate lines of animals with very specific addiction profiles. Examples include differences in drug preference, sensitivity, tolerance, dependence and withdrawal symptoms.

Today researchers are still studying some of these same animal lines and strains. For example, Dr. Scott Rogers is studying different strains of mice (right) that vary in their addiction potential for alcohol. By identifying the genes responsible for this vulnerability in mice, researchers hope to identify homologous genes in humans that render a person more or less susceptible to alcohol addiction.