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can approve the experiment. The safety of human subjects is paramount, and the benefits from the research must outweigh any risks to the subjects. There are federal regulations for the protection of human research subjects (45 CFR 46, 42 CFR 52h, Public Law 103-43) that are strictly enforced. The guidelines for administration of drugs to human subjects can be found at http://www.drugabuse.gov/Funding/HSGuide.html .
    2 The National Research Council has published the
Guide for the Care and Use of Laboratory Animals,
Eighth Edition (Washington DC: The National Academies Press, 2011), which is strictly enforced at the national level. Any investigator using animals must justify the species and numbers, provide adequate veterinary care, describe provisions for minimizing discomfort and distress, and provide euthanasia if needed.
    3 For example, two papers that show this are as follows: Ahmed, SH and George Koob. “Long-Lasting Increase in the Set Point for Cocaine Self-Administration after Escalation in Rats.”
Psychopharmacology
146:303-312, 1999. Paterson, NE and A Markou. “Increased Motivation for Self-Administered Cocaine after Escalated Cocaine Intake.”
Neuroreport
14:2229-2232, 2003.
    4 See endnote 1.
    5 Lundahl LH and CE Johanson. “Cue-Induced Craving for Marijuana in Cannabis-Dependent Adults.”
Exp Clin Psychopharmacol
19:224-230, 2011.

3. Feeling Good: The Brain’s Own Reward System
    What do drugs do for us? An addict was asked why she injects heroin. Her reply was that it is like a dozen orgasms! Although the effects can vary according to the drug, it is safe to say that drugs can make us feel good, or even wonderful. The concepts of pleasure, reward, and reinforcement are so important for drug abuse that we can’t leave this topic without describing key discoveries about the brain’s own pleasure and reward system. Drugs couldn’t produce reward if these capabilities weren’t already in the brain.
    Prior to experiments showing a drug-related reward described in the previous chapter, there were experiments that revealed a naturally occurring reward and reinforcement system in the brain. Given that the brain works partly by electrical activity, it isn’t surprising that these discoveries relied on electrical stimulation of brain regions. If you carry out an action that results in an immediate reward or good feeling, you want to carry out that action again and again, and we all do this every day. The good feelings reinforce (and hence, the idea of “reinforcement”) the performance of the actions that produced them. For example, we get to the dining room in time for meals. We learn, develop habits, and so on, in response to rewards. Given that the brain is the organ of behavior, how do we find out where these rewarding and reinforcing actions reside in the brain and what exactly happens in the brain?
    To answer these questions, electrodes can be implanted in the brain, stimulated, and the elicited behaviors can be recorded and measured. However, there is also a procedure called electrical
self
-stimulation, which is the process by which rats (and humans) press a lever that delivers an electrical stimulation to some part of the brain. Yes, lever pressing again! Only this time it is not a drug injection but rather a direct electrical stimulation of the brain that is the result. The fact that the animals press the lever again and again means that there is something positive or good about the result of electrical stimulation. But electrical self-stimulation occurs only when the electrodes are in certain parts of the brain, revealing to us the parts of the brain that are involved in giving us rewards or pleasure. This was an important discovery that was made in the 1950s.
Superb Observers and a Big Discovery
    Here’s how it all started. In 1954, two young scientists, Drs. James Olds and Peter Milner, were trying to find out whether electrical stimulation of a part of the brain called the reticular formation