Self-administration
Self-administration of putatively addictive drugs is considered one of the most valid experimental models to investigate drug-seeking and drug-taking behavior.
Self-administration of addictive drugs has been studied using humans,[1] non-human primates,[2] mice,[3] invertebrates such as ants, and, most commonly, rats.
During the task, animal subjects are operant conditioned to perform one action, typically a lever press, in order to receive a drug.
Spragg was one of the first researchers to create a model of chronic morphinism in a chimpanzee to explore the role of operant conditioning in relation to a drug dependency.
[6] Weeks (1962) published an account of the first true use of the intravenous self-administration paradigm in a study aiming to model morphine addiction in unrestrained rats.
For the first time, an addictive substance served as an operant reinforcer and rats self-administered morphine to satiety in stereotyped response patterns.
[7] The scientific community quickly adopted the self-administration paradigm as a behavioral means to examine addictive processes and adapted it to non-human primates.
In light of these similarities between the different animal models, it was identified that the addictive potential of psychoactive substances could be investigated using rats instead of nonhuman primates.
Although not always required, subjects may be first pre-trained to perform some action, such as a lever press or nose poke to receive a food or water reward (under food- or water- restricted conditions, respectively).
Humans suffering from addiction often resort to intravenous drug use for similar reasons, so this route of administration increases the face validity of the construct.
The number of operant responses required per unit of reinforcer may be altered after each trial, each session, or any other time period as defined by the experimenter.
The catheter is secured to the animal by a harness or backplate and is tethered to a protective leash that extends upward through a hole in the top of a chamber, where it attaches to a rotating swivel on a mechanical arm that allows the subject to move around freely.
The sterile intravenous catheter used to deliver the drug into the bloodstream of the subject is typically composed of flexible plastic, silastic tubing, and nylon mesh placed subcutaneously.
Conducting self-administration studies in animal models provides a much greater level of experimental flexibility than in humans because investigating the effects of novel pharmacological drug treatments poses significantly fewer ethical and practical barriers.
In 1999, Pilla and colleagues published in Nature a study documenting the efficacy of a partial D3-agonist (BP-897) in reducing environmental cue-induced cocaine craving and vulnerability to relapse.
[23] A 2010 study published in Nature showed an upregulation of microRNA-212 in the dorsal striatum of rats previously exposed to cocaine for extended periods.
The authors of the study noted that viral-infected animals exhibited decreased operant responding during the post-infusion time-out period and proposed that this demonstrated a reduction in compulsive drug-seeking behavior.
2) Resistance to punishment: Measured by how much rats maintain rates of self-administration when cocaine infusion is paired with an electric shock.
The researchers used an additional test to further support the classification of a rat as “addicted” by measuring relapse rates during reinstatement paradigms.
Self-administration experiments can also be paired with methods such as in vitro electrophysiology or molecular biology to understand the effects of addiction on neural circuitry.
The use of the self-administration methodology to model human drug addiction provides powerful insight into the physiological and behavioral effects of the disease.
