reward and compulsion

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Brain reward systems and compulsive drug use
Paul J. Kennya, aDepartment of Biochemistry, The Scripps Research Institute, Jupiter, FL 33458, USA Available online 5 February 2007.

Compulsive drug intake is a hallmark of addiction, yet a mechanistic understanding of this process has been elusive. Drug use is initiated primarily to obtain the excitatory actions of addictive drugs on brain reward systems. Paradoxically, excessive drug intake can decrease the activity of reward systems, reflected in elevated intracranial self-stimulation thresholds in rats, probably by engaging compensatory mechanisms to counter drug effects. Recent evidence suggests that compulsive drug intake might develop in response to such adaptive decreases in brain reward systems. Further, the actions of addictive drugs on reward systems are susceptible to classical conditioning processes, providing a potential mechanism by which drug-paired stimuli can induce powerful cravings and precipitate relapse in abstinent drug users. These findings provide a conceptual framework for improving our understanding of compulsive drug use, and might facilitate the development of novel therapeutics for substance abuse disorders.

Glossary

Action–outcome (goal-directed) responding
behavior directed toward achieving a goal, and is under voluntary control (i.e. sensitive to the relative value of the goal). Action-outcome responding is dependent upon the animal learning the causal relationship between its actions and the likelihood of achieving the goal.

Classical conditioning
originally characterized by the Russian physiologist Ivan Pavlov, and involves the learning process in which a previously neutral environmental cue (CS) can attain motivational salience and elicit a conditioned response after being repeatedly associated with an intrinsically salient stimulus (unconditioned stimulus; US) that induces an automatic response (unconditioned response). In our experiments, a CS (previously neutral flashing light and tone) is repeatedly paired with a US, usually a drug of abuse or a receptor antagonist that precipitates withdrawal in drug-dependent animals, during daily conditioning sessions. The CS can eventually elicit responses similar to those induced by the US.

Escalation of drug intake
in rats is the process by which extended daily access to a drug results in the gradual increase of drug intake over time, a process reminiscent of the loss of control over intake usually observed in human drug addicts.

Intracranial self-stimulation (ICSS)
a behavioral procedure that provides a sensitive measure of the effects of addictive drugs on brain reward systems. Rats turn a response wheel to receive electrical pulses directly into their brain through indwelling stimulating electrodes located within components of the reward system of the brain. In our experiments, the stimulating electrode is located within the posterior lateral hypothalamus, targeting the medial forebrain bundle. The intensity of the electrical pulse is varied (according to the method of limits), such that the minimal electrical intensity (termed the ‘reward threshold’) for which the animal is prepared to respond can be identified for each rat. Acute administration of major drugs of abuse lowers the reward threshold, whereas withdrawal from addictive drugs after chronic administration usually elevates the reward threshold.

Precipitated withdrawal
the process by which withdrawal might be transiently ‘precipitated’ in drug-dependent animals (or humans) by administration of a compound that antagonizes the actions of that particular drug. For example, withdrawal might be precipitated in opiate-dependent rats by administration of the opioid receptor antagonist naloxone.

Reinforcer
an object or event that is obtained or that occurs in response to a particular behavior, is contiguous with that behavioral response in a temporal and spatial manner and is associated with an increased probability that the behavior response will occur again. Put simply, a reinforcer is anything that increases the likelihood that a given response will be repeated.

Stimulus–response (habit) responding
usually emerges after goal-directed responding has been repeated on many occasions, until such responding becomes more habitual and sensitive to goal-associated conditioned stimuli, and less under voluntary control (i.e. insensitive to the relative value of the goal).