Behavioral pharmacology and substance abuse

Behavioral pharmacology and substance abuse
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  260  Behavioral Pharmacology and Substance Abuse These pesticides were not designed with hon-eybees in mind. In fact, the chemists at Bayer did not intend for honeybees to be affected at all.These pesticides are designed to weaken the insects’ natural defenses against disease and other infectious organisms. In this way, these pesticides attack the insects naturally and are not a danger to the overall ecosystem with harsh chemicals. However, studies have shown that these pesticides are affecting honeybees.The result for the honeybee colonies is a phenomenon known as honeybee colony col-lapse. In essence, exposed honeybees bring the neonicotinoids back to the hive. From there, the pesticide is passed along to the other bees in the colony. The overall weakening of natu-ral defenses against infection occurs through-out the colony and leads to the eventual decline and collapse of the honeybee colony. Honeybee colony collapse is a syndrome that entomologists and chemists are scrambling to address. Bayer denies that their pesticide was designed to affect honeybees, or is possibly causing honeybee colony collapse.As a result, apiarists (beekeepers) in both the United States and Canada have filed sepa-rate civil suits against the Bayer Chemical Company. These suits allege that the Bayer Chemical Company is responsible for negli-gence in developing and marketing these pesti-cides. These individual suits are demanding a cease and desist in the manufacturing and marketing of the neonicotinoids pesticides. Also, the suits are seeking compensation for damages and lost revenue due to honeybee colony collapse.Also, the U.S. Environmental Protection Agency (EPA) has issued a warning to farmers and other agricultural workers regarding the damages neonicotinoids present for honey-bees. Similarly, the European Commission has recently restricted the use of these types of pesticides in countries belonging to the European Union. While the commission had restricted the use and the EPA has issued a warning, some agricultural professionals continue to utilize these pesticides. Until con-clusive evidence is found linking Bayer’s neo-nicotinoids with the phenomenon known as honeybee colony collapse, and the lawsuits are settled, their use on crops continues.R. Casey Davis Independent Scholar See Also:   Antipyretic Drugs; Germany; History of Pharmacology: Europe; Pharmaceutical Law. Further Readings Bayer. [Web site] (Accessed April 2, 2015).Hayes, Peter. Industry and Ideology: IG Farben in the Nazi Era . New York: Cambridge University Press, 1987.Mahdi, J. G., A. J. Mahdi, A. J. Mahdi, and I. D. Bowen. “The Historical Analysis of Aspirin Discovery, Its Relation to the Willow Tree and Antiproliferative and Anticancer Potential.” Cell Proliferation , v.39/2 (April 2006).Mann, Charles C. and Mark G. Plummer. The Aspirin Wars: Money, Medicine, and 100 Years of Rampant Competition . Boston: Harvard Business School Press, 1991. B EHAVIORAL  P HARMACOLOGY     AND  S UBSTANCE  A  BUSE Behavioral pharmacology is the scientific field in which research is conducted on the contri-bution of drug effects to behavior and the interactions between behavior and drugs. The term was coined by Peter Dews in the 1950s and is interchangeable with the term  psychopharmacology , a term that was used previously by David Macht in the 1920s. Copyright © 2015 SAGE Publications. Not for sale, reproduction, or distribution.  Behavioral Pharmacology and Substance Abuse 261 Travis Thompson and Charles Schuster authored the first book devoted to behavioral pharmacology in 1968. The field involves three dominant goals: (1) to develop and evaluate behavioral interventions that can have an impact in screening the effectiveness of drugs, (2) to investigate how behaviorally active drugs are implemented using behavioral techniques, and (3) to use drugs as a tool for analyzing complex behavioral processes. Methodological Considerations Methodologically, this area of research uses mainly experimental techniques and, lately, behavioral neuroscience techniques. Research-ers try to understand the association between a drug dose and behavioral processes within human beings and/or animals. Various experi-mental designs can be used to permit compari-sons between the state of an organism when the drug is given and the state of the organism when the drug is absent. In a randomized experiment, subjects are assigned, using a ran-dom process, to different groups, with each group having a different experimental condi-tion, such as being administered different drugs. Often one group, called a control group, receives no treatment, or a placebo treatment; in the latter case, the group receives an inactive drug or other nontreatment that is disguised to look like a treatment. Sometimes experimental designs include all these ele-ments: groups assigned different drugs or treatments, one group assigned a placebo, and one group receiving no treatment at all. The key in experimental designs is that the researcher controls which groups receive which treatments (although subjects are often randomized into the groups).Less frequently, a nonexperimental design is used. In a nonexperimental design, the researcher looks at the association between factors and outcomes, such as alcohol con-sumption and depressive symptoms, as they occur naturally, rather than assigning (for instance) one group to consume alcohol. The difference between experimental and nonex-perimental research is that in the latter, no condition is manipulated. Nonexperimental designs are commonly used when it would be impossible or unethical to assign conditions to participants. For instance, gender is often a factor of interest, but it is not possible to assign humans to genders. As another example, often tobacco consumption is included as a factor in medical studies, but it would not be ethical to assign subjects to smoke or otherwise consume tobacco, because it is harmful to health.One new methodology used within behavioral pharmacology and substance abuse is that of behavioral neuroscience techniques. The use of neuroscience techniques in behavioral pharmacology is based on the assumption that prolonged use of drugs has an impact on the functionality and structure of the brain. The most common brain imaging techniques used to assess the impact of drug use in the brain are positron emission tomography (PET), single-photon emis-sion computed tomography (SPECT), and func-tional magnetic resonance imaging (fMRI).PET produces three-dimensional brain images using radioactive tracers (chemical compounds used to identify the mechanisms of chemical reactions) and following the paths in the brain of various radioisotopes, such as oxygen, nitro-gen, carbon, and fluorine. PET is used to mea-sure the brain distribution of stimulant drugs (methamphetamines, amphetamines, cocaine), opioids (heroin, morphine), hallucinogens (such as ketamine), and other drugs, such as mari-juana, alcohol, and nicotine. It can also be used to measure receptor density in specific brain areas after administering radiotracers, to mea-sure potential competition between radiotracers with neurotransmitters, to identify which brain Copyright © 2015 SAGE Publications. Not for sale, reproduction, or distribution.  262  Behavioral Pharmacology and Substance Abuse areas are active during drug-related activities, and to make preliminary observations of devel-oping drug treatments in animals. The main limitation of PET is that it has a low degree of spatial resolution, and therefore SPECT can be used as an alternative. The process of undertak-ing analysis using SPECT includes the adminis-tration of gamma rays through a collimator and the use of other radioisotopes, such as xenon, iodine, and technetium.fMRI is based on the principles of magnetic resonance imaging, whereby an external mag-netic field is created, forcing the hydrogen nuclei within the body to be aligned along the direction from head to toe (the z-axis) while spinning hydrogen protons rotate. Together with this magnetic procedure, another proce-dure (resonance) transfers electromagnetic energy as radiofrequency waves into the body. Finally, the spin-echo sequence allows three-dimensional images to be constructed. In neu-roscience, fMRI is used, with the use of a magnetic metal called gadolinium allowing the projection of specific brain regions that are activated by a stimulus (drug). Substance Abuse Behavioral pharmacology also aims to provide an answer to the question of why people use or abuse drugs. Current research focuses not only on addictive patterns of behavior (alcohol, smoking, heroin, etc.) but also on societally acceptable types of drug use (such as coffee con-sumption). The Diagnostic and Statistical Manual of Mental Disorders  ( DSM ) of the American Psychiatric Association uses the terms substance dependence  and substance abuse  when referring to addictive behaviors and pro-vides a set of criteria for diagnosis. Substance abuse is defined in DSM-IV-TR  as a maladap-tive pattern of substance use leading to clinically significant impairment or distress, as manifested by one (or more) of the following, occurring within a 12-month period: (1) recurrent sub-stance use resulting in a failure to fulfill major role obligations at work, school, or home; (2) recurrent substance use in situations in which it is physically hazardous; (3) recurrent sub-stance-related legal problems; and (4) continued substance use despite having persistent or recur-rent social or interpersonal problems caused or exacerbated by the effects of the substance.When an individual uses drugs repeatedly and for a prolonged time, tolerance may result. Drug tolerance is defined as a diminished response to the administration of a drug after repeated exposure. Tolerance can also decrease the effectiveness of another drug. For example, patients with chronic alcohol problems experi-ence greater effects of an anticonvulsant dose of phenobarbital. Tolerance in general can be reversed when the drug is stopped; it also varies among different drugs and can occur rapidly, less rapidly, or never. In addition, the develop-ment of tolerance depends on the drug dose and frequency of use as well as the drug-taking environment. Metabolic or disposition toler-ance is defined as a reduction in the amount of drug available at the target tissue after repeated drug use. Pharmacodynamic tolerance is the most severe form of tolerance and is defined as changes in nerve cell function caused by repeated use of a drug. Finally, behavioral or context-specific tolerance occurs when toler-ance happens in one environment but is reduced or eliminated in a new environment.Behavioral pharmacology since the early 20th century has used the dependence model to explain substance abuse. This model suggests that substance abuse can result from negative reinforcement; for example, individuals addicted to drugs can use drugs to avoid certain unpleas-ant situations, such as withdrawal. Withdrawal is defined as an individual’s unpleasant condi-tion when the effect of a drug is gone, and the Copyright © 2015 SAGE Publications. Not for sale, reproduction, or distribution.  Behavioral Pharmacology and Substance Abuse 263 concept has been used to explain the addictive use of drugs such as opioids and alcohol. There-fore, an individual becomes physically depen-dent on a drug and compulsively self-administers the addictive substance to avoid withdrawal symptoms. Withdrawal symptoms are defined as the physiological changes that occur when an individual stops using or decreases use of a drug. They occur a few hours after a drug is stopped. In contrast, some evidence exists that several addictive substances (such as marijuana) produce mild withdrawal symptoms when stopped, and therefore dependence alone can-not fully explain substance abuse. Furthermore, the DSM-5  has redefined dependence in order to not incorrectly define individuals who become physically dependent on their prescribed medications.The psychological parameters of depen-dence have also been used to explain substance abuse. Even though they are not measurable, the psychological consequences of withdrawal are widely believed to make a significant con-tribution to substance abuse, and evidence from research on smoking cessation outlines the psychological aspect of addiction to nicotine. Others are skeptical about using psychological dependence to explain substance abuse, because of conceptual problems that lead to confusion when it comes to causality-outcome associations. They suggest that it is difficult to ascertain whether psychological dependence is the predictor or the outcome of drug use. However, evidence using neuroscien-tific imaging methods suggests that prolonged drug use creates severe neurological changes in the brain, such as in its neural circuitry. Behavioral Pharmacology and Substance Abuse Several theorists have suggested that the desire to change the state of consciousness can be an explanation for substance abuse. This theory is also based on the assumption that only humans present addictive behaviors. There were several attempts in the early 20th century to induce addiction in animals, but researchers were not successful, because animals make use of condi-tioned taste aversion, which protects them from any substances that create problems such as sickness. However, when animals consumed substances such as morphine, they became physically dependent, but again, the animals would not seek the substances when they were given the choice not to consume them. There-fore, substance abuse as a psychological drive is a human characteristic.The opponent process theory suggests that substance abuse stimulates euphoria followed by dysphoria and resulting compensatory responses such as perceived noise or sensitivity to light. This state is often mistakenly associated with the term hangover . Specific substances are found to create severe compensatory responses that follow the opponent process: cocaine cre-ates depression, and chlordiazepoxide creates anxiety. Compensatory responses are experi-enced as withdrawal symptoms when the drug is stopped after a period of time. Therefore, the organism is making drug-induced alterations to compensatory changes in order to return to “normality.”The principles of classical conditioning and operant conditioning have been used to explain substance abuse. Classical conditioning is based on the experiments of Ivan Pavlov, which showed that an unconditioned stimulus (the drug) provided to a dog together with a conditioned stimulus (a sound) led to the dog’s experiencing the unconditioned response of the drug (salivation and vomiting) in the absence of the drug (conditioned response). However, today it is known that the condi-tioned response can be very different from the unconditioned response produced by a drug. Copyright © 2015 SAGE Publications. Not for sale, reproduction, or distribution.  264  Behavioral Pharmacology and Substance Abuse Experiments by Shepard Siegel have demon-strated that the environment associated with substance abuse creates physiological changes that are opposite to the substance’s effects. Similarly, evidence exists showing that classi-cal conditioning can be applied to withdrawal symptoms. Operant conditioning is based on the “Skinner box” experiment and suggests that learning is mediated by reinforcement or punishment.The positive reinforcement model of substance abuse suggests that substances are initially always self-administered. Positive rein-forcement   refers to a state of pleasure, but positive reinforcers do not always cause plea-sure. Positive reinforcement has been associ-ated with activity in specific brain regions. The self-administration experiments that have been conducted using humans and animals to con-firm the role of positive reinforcement in sub-stance abuse have offered a rich understanding of drug use and drug abuse. Similarly to the psychological dependence model, the positive reinforcement model has been criticized for the circularity of its logic, which is the assump-tion that a drug is a positive reinforcer and is affected by the assumption that drug use increases addictive behavior.Placebo experiments, in which humans’ rates of responding or amounts of consump-tion and progressive ratio schedules were mea-sured, have provided important evidence on the capacity of substances to act as positive reinforcers. First, there is variability among different types of substances in whether they can act as positive reinforcers (called abuse potential or abuse liability). Cocaine and psy-chomotor stimulants were found to be the strongest reinforcers. Second, a higher dose of a drug has not been confirmed as an absolute predictor of reinforcement, because some studies have shown that higher drug doses lead to more reinforcement, whereas others have shown the opposite. Third, genetic predispositions can explain drug abuse, espe-cially alcohol and cocaine. Fourth, patients who use substances for the relief of disease symptoms (i.e., pain) can experience the rein-forcing effect of the drugs. Fifth, humans’ decisions to use substances can depend on expected demands (i.e., driving). Sixth, stress has been found to be a detrimental factor in substance abuse, especially for alcohol, cocaine, and opiates. Finally, other evidence of drugs’ capacity as positive reinforcers includes previous experience with a specific drug, the presence of withdrawal symptoms, extended use of a drug (especially cocaine), and the priming effect of drugs. Psychoneuroendocrinology of Substance Abuse Neuroscience and brain imaging techniques, as well as endocrinological research, have pro-vided evidence of specific brain regions that are changed or disrupted because of prolonged substance abuse. The mesolimbic dopamine system is shown to be activated by the use of cocaine, amphetamines, heroin, morphine, nicotine, and alcohol. As a result of dopamine excretion, the stimuli are enhanced and acute reinforcing effects are mediated while the sub-stance abuser can reuse a drug to mediate dopamine activity and return to a normal state.However, these endocrinological changes cannot fully explain long-term substance abuse. Therefore, research has moved further to investigate the brain regions that are con-nected with dopamine neurons and that are also connected with one another by glutama-tergic projections. These brain regions experi-ence neuroplastic changes caused by substance abuse and causing substance abuse–related behaviors. Examples of such brain regions Copyright © 2015 SAGE Publications. Not for sale, reproduction, or distribution.
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