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Addiction and the Animal Model

Human Head

What is addiction?

The American Society of Addiction Medicine defines addiction as "...a primary, chronic disease of brain reward, motivation, memory and related circuitry. Dysfunction in these circuits leads to characteristic biological, psychological, social and spiritual manifestations. This is reflected in an individual pathologically pursuing reward and/or relief by substance use and other behaviors."

There are many different forms of addiction. Whether it's an addiction to drugs, alcohol, sex, gambling, or even food or shopping, they all operate under the same chemical mechanism in the brain.

How does addiction work?

Addiction works by triggering neurotransmitters, namely dopamine, in the pleasure centers of the brain. Changes in the nucleus accumbens, forebrain, and anterior cingulate cortex, among others, are common in areas affected by these chemical releases that occur in the brain during the addictive cycle.

The addictive cycle is one where at first the user maintains they are free to choose when they use. As changes in the brain grow, there becomes less choice and the user feels compelled to use to feel good. This is dependency and the beginning of the addiction cycle. As the user develops tolerance, it becomes necessary to use more in order to get the same original good feeling. At this point, the user either gets help to break the addiction or begins spirally out of control, even doing things detrimental to their well-being in order to maintain.

Once the cycle is broken for whatever reason, users go through a period of withdrawal as the brain and body adjust back to a non-drug state. Withdrawal is often characterized by physical symptoms not normally manifested while the drugs are being used. Because addiction causes physiological changes in the brain, users often feel cravings even after many years of disuse. These cravings often cause users to relapse.

Addiction in the animal model.

mouse in cage

Researchers have long been using animal models, namely rats, mice and primates, to mimic addiction models in humans. Rodents and primates suffer addiction and brain changes similar to human models, and so, can be suitable replacements for them in study. Examples of drugs often chosen for animal models include nicotine, alcohol, cocaine and heroin.

Addiction studies, accomplished through self-administration, is a form of operant conditioning. Animals are placed inside an operant chamber where they are trained to press a lever for a reward. Once the animal is properly conditioned, they can easily be switched from something simple, like a food reward, to a drug reward. Animals then receive a dosage of drug whenever they press the lever, “self-administering” the drug.

Drugs are most often delivered intravenously through a catheter mounted on the animal’s back. These catheters are generally made with a small stainless steel tube bent in a “U” shape and have a small piece of mesh fabric made onto them. The animal’s skin grows into this mesh as the animal heals from the implantation surgery, and this helps to secure the catheter in place. Commercial catheters have a molded plastic piece on them for connection of mating tethers. Polyethylene or silastic tubing is attached to each side of the catheter; one piece runs into the animal’s jugular vein, the other piece runs to a syringe pump. The pump connects directly to one of the levers in the operant chamber.

Self-administration easily pairs with other types of study including electrophysiology and microdialysis. These can help researchers determine level of addiction, withdrawal, as well as efficacy of treatment options. Addiction treatments such as methadone and nalprexone were both developed using the self-administration model.

P1 Technologies has been making backmount catheters for self-administration work for many years. Contact our engineers to help with your experimental design today!

By: Aubrey Shifflett