Glossary of Terms

2′ Methylnicotine
During the discrimination and prostration tests he conducted at Philip Morris during the early 1980s, Dr. Victor DeNoble identified the man-made chemical 2′-methylnicotine (pronounced two-prime methyl-nicotine) as the most effective nicotine analog, causing rats to behave as if they were getting a nicotine high but without signs of heart distress, like a rapid heartbeat, that usually follow nicotine use.
Acetaldehyde is an intermediate by-product in normal carbohydrate metabolism, and a natural product of burning sugars and other materials in the tobacco leaf used in cigarettes. The role of reducing sugars – any sugar that either has an aldehyde group or is capable of forming one in solution through isomerisation – predominant in many flavor additives to tobacco products leads to the production of increased levels of acetaldehyde that enhance dependence as well as toxicity. The application of flavor additives was a long-standing industry practice, dating back to the addition of molasses to burley tobacco in the 19th century to create “American” blended tobacco.
In chemistry, a structural analog, also known as chemical analog or simply analog, is a compound having a structure similar to that of another one, but differing from it in respect of a certain component, such as one or more atoms, functional groups, or substructures. Despite a high chemical similarity, structural analogs are not necessarily functional analogs and can have very different physical, chemical, biochemical, or pharmacological properties. In drug development large series of structural analogs of an initial lead compound are created and tested as part of a structure-activity relationship study.
Behavioral Pharmacology
Pharmacology is the study of how drugs act on biological systems, focusing on how a drug gets into the body, where in the body the drug acts, and how the body gets rid of a drug. The basis for the behavioral pharmacology discipline is the effect of drugs on behavior, including preclinical and clinical studies – the former frequently performed with rats – that try to understand why people become addicted to drugs like alcohol and cocaine.
Controlled Substance
A controlled substance is a drug which has been declared by federal or state law to be illegal for sale or use, but may be dispensed under a physician’s prescription. The basis for control and regulation is the danger of addiction, abuse, physical and mental harm, including death. Self-administration is the test that the Food and Drug Administration, the Drug Enforcement Administration, and the National Institute of Drug Abuse use to decide whether or not to label a drug as a controlled substance.
In descrimination studies, effects of drugs serve as discriminative stimuli that indicate how reinforcers (e.g. food pellets) can be obtained. For example, animals – most commonly rats – can be trained to press one of two levers to obtain food after receiving injections of a drug, and to press the other lever to obtain food after injections of the vehicle. After the discrimination has been learned, the animal starts pressing the appropriate lever according to whether it has received the training drug or vehicle. Led by Dr. Victor DeNoble’s pioneering research at Philip Morris, preclinical drug discrimination techniques have played a significant role in advancing our knowledge of the receptor mechanisms underlying the interoceptive effects of nicotine.
Dopamine is a neurotransmitter present in a wide variety of animals, including both vertebrates and invertebrates, that either increases or reduces the activity of neurons (nerve cells). It has a variety of influences on brain function, including playing a role in regulating attention, cognition, movement, pleasure, and hormonal processes. All substances that trigger dependencies in human beings increase the release of dopamine. Nicotine, like other drugs, causes a sudden surge of dopamine, but the surge quickly gives way to plummeting dopamine levels, which makes smokers feel bad and crave another cigarette.
A neurotransmitter is a chemical substance that’s released at the end of a nerve fiber by the arrival of a nerve impulse and, by diffusing across the synapse or junction, causes the transfer of the impulse to another nerve fiber, a muscle fiber, or some other structure.
Prostration is the placement of the body in a submissively prone position. Dr. Victor DeNoble’s landmark 1982 study, BEHAVIORAL EFFECTS OF INTRAVENTRICULARLY ADMINISTERED (-)-NICOTINE ON FIXED RATIO SCHEDULES OF FOOD PRESENTATION IN RATS, describes the “prostration syndrome” in rats injected with nicotine.
In the physiology of the brain, a receptor is a molecule in a cell membrane that responds specifically to a particular neurotransmitter. The nicotine molecule is very similar in shape to a neurotransmitter called acetylcholine, which affects many bodily functions, including breathing, heart rate, learning and memory. Acetylcholine in turn also affects other neurotransmitters that have influence over appetite, mood, and memory. When nicotine enters the brain, it binds to a particular type of acetylcholine receptor, known as the nicotinic receptor, and attaches to nerve cells in places where acetylcholine would, creating the same effects.
In animal experimentation, most commonly using rats or mice, self-administration is a form of operant conditioning where the reward is a pharmacological substance. This drug can be administered remotely through an implanted intravenous line or injected directly into the ventricular system of the brain. Self-administration of putatively addictive drugs is considered one of the most valid experimental models to investigate drug-seeking and drug-taking behavior. The higher the frequency with which a test animal emits the operant behavior, the more rewarding, and possibly addictive, the test substance is considered.