Nonhuman models

How do we study drug taking behaviors in nonhuman animals?

Answer: A self administration paradigm can be used to assess drug taking behavior in nonhuman animals.



One common method for studying drug taking in animals is to have them perform a behavioral assay called self administration. In this experimental paradigm, a cohort of animals undergo a surgery to allow the direct administration of some drug into their body. For example, an intravenous catheter may be placed directly into the circulatory system, and the drug can be delivered directly into the bloodstream. Alternatively, an intracranial catheter can be put into the brain.

Drug self administration is generally used to study drug seeking behaviors in nonhuman primates or in rodents such as mice or rats. Just like in human addicts, these animals will increase their use of the drug over time, as they learn to give themselves more drug over time. They will also tend to work harder for the drug, as measured by a progressive ratio drug delivery schedule.

The animal is placed into a box. Inside the box, there are two specific components with which the animal can interact. There is an active lever and an inactive lever. A computer counts the number of times each lever is pressed. When the active lever is depressed, an infusion of drug is delivered. When the inactive lever is pressed, they may receive an infusion of the vehicle, which is often saline. Pressing the lever is an operant response, since this behavior can be altered with a drug reinforcer.

Instead of levers, animals may also perform the same drug seeking behavior using nose pokes as the operant response. In this variation, two small holes are presented. The holes have laser beams across the entrance. When the path of these laser beams is broken, the computer records this as a nose poke. As with lever pressing, there is also often an inactive nose hole, where a nose poke will be recorded but no reward will be delivered.

With drug self administration, animals must often be trained on the device before they will lever press or nose poke. Usually, this means restriction the animal’s access to food until they are at some less than optimal body weight, then rewarding them with delivery of a food pellet after they press on the lever. Over a few sessions, the food reinforcer is switched for the drug reinforcer.

An animal that finds the effect of the drug to be rewarding will repeatedly press the lever or nose poke more frequently than one that does not perceive a rewarding effect. Rats and mice will self administer many drugs of abuse, including cocaine, heroin, and nicotine. They often do not self administer psychedelic drugs such as LSD.

This operant responding can be modified by other pharmacology. For example, giving the animal an opioid antagonist will decrease their number of active responses in a heroin self administration paradigm.