Animal models of substance abuse and addiction: implications for science, animal welfare, and society

Abstract

Substance abuse and addiction are well recognized public health concerns, with 2 NIH institutes (the National Institute on Drug Abuse and the National Institute on Alcohol Abuse and Alcoholism) specifically targeting this societal problem. As such, this is an important area of research for which animal experiments play a critical role. This overview presents the importance of substance abuse and addiction in society; reviews the development and refinement of animal models that address crucial areas of biology, pathophysiology, clinical treatments, and drug screening for abuse liability; and discusses some of the unique veterinary, husbandry, and IACUC challenges associated with these models.

Figure 1.

A glossary of some terms used in studying drug reinforcement. Based on information in reference 71.

Figure 2.

Use of an operant chamber for a rodent intravenous drug self-administration paradigm. Rats are implanted with chronic, indwelling catheters in the jugular vein. The catheter exits the rat on the dorsum, where it is connected to a tether-and-tubing system that is attached to a drug-loaded syringe. Responding on the active lever leads to infusions of the drug.

Figure 3.

An example of using the extended-access drug self-administration procedure to predict vulnerability, in this case sex differences in levels of cocaine intake. (Left) Male and female rats were compared in their responses for cocaine under extended access conditions by using a discrete trial procedure (4 trials/h, 1.5 mg/kg/infusion). Results show that female rats take more cocaine over a 10-d access period as compared with male rats. (Right) When responding is assessed 10 d after extended-access cocaine self-administration, female but not male rats show enhanced levels of progressive-ratio responding as compared with female and male rats tested after short-access cocaine self-administration (for example, maximum of 20 infusions/d for 5 d). n = 7 to 12. *Significant (P < 0.05) difference between male and female rats.

Figure 4.

Alcohol dependence withdrawal scoring. This scoring sheet is useful for determining the time course of the alcohol withdrawal syndrome. Animals are scored based on presence and severity of above clinical manifestations. A total score ≥ 3 indicates signs of withdrawal. Higher scores signify peak expression of withdrawal. A low score is indicative of an animal at the beginning or end stage of withdrawal or lack of dependence induction.