Biology 202, Spring 2005
Third Web Papers
On Serendip

Most current definitions of drug addiction focus primarily upon behavioral abnormalities. Changes such as loss of control over the intake of a drug or drugs and continuing to take drugs without regard to the detrimental side effects typically define behavior of an addict (7). Unfortunately for individuals suffering from addiction society often regards behavioral issues as weaknesses that should be modified by the sufferer, without regard to the chemical changes perpetuating the addiction. These problems often fall into the same category as depression where people simply do not discuss the psychological "weakness," expecting the sufferer to 'snap out of it.' Current research focuses on the molecular and structural drug-induced neural plasticity responsible for the behavioral changes of addicts. In the view of researchers studying the molecular changes of behavioral modification, repeated exposure to controlled substances can alter the amounts and types of genes expressed in different areas of the brain. These changes in gene expression occur by perturbations in the regulation of gene transcription. The altered expressions of these genes affect the functioning of individual neurons and the circuits of which they are a part (7). Other researchers focus on structural changes of the brain to explain the behavioral changes caused by addiction. The research in this area provides evidence for the fact that repeated exposure to drugs of abuse creates structural changes involving reorganization and branching of neurons. These changes mimic those seen as a result of learning and memory (8). The reorganization and structural changes of the neurons affect the functioning of routine neuronal impulses, thus modifying normal behavioral patterns. This case relies upon behavioral or psychological impetus to produce substance abuse and provides no physiological explanations for the beginnings of abuse. The structural changes merely display a physical representation of the behavioral changes associated with addiction.

Scientists do not yet fully understand the mechanisms behind addiction or the brain's response to stimulation and rewards. However, the effects of drugs compare to those seen by electrical stimulation of the hypothalamus and surrounding structures. Ordinarily, rewards only possess effectiveness if the brain of an individual is in a drive state. For example, food represents a reward only if the individual receiving it feels hungry. The rewards of electrical stimulation work independently of the drive state of the brain. Electrical stimulation goes as far as to create a drive state even if a need for a drive does not exist, as well as using neural circuits normally activated by the stimulus of a reward. Trained to self administer intracranial electrical stimulation, laboratory rats often choose activation of the electrical pulse over normal physical rewards of food or sex. Stimuli activate dopaminergic neurons in the hypothalamus causing increased output of dopamine in the synapses between these neurons in the mesolimbic dopamine system. Currently, most believe the mesolimbic dopamine system regulates the signals responsible for controlling biological drives and motivation (4). For example, this system possesses the responsibility of regulating the sensation of hunger as well as producing the drive necessary to induce eating in an organism and the reinforcement gained by eating. While electrical stimulus can create a larger than normal opportunity for release of dopamine, addictive drugs increase the rewarding effects caused by electrical stimulation. Drugs such as cocaine, amphetamines, narcotics, and nicotine all function as positive reinforcers in the mesolimbic dopamine system by facilitating transmission of dopamine (4).

Psychoactive drugs increase the level of dopamine released at the synapse of the dopaminergic neurons by blocking the dopamine transporters thereby causing the dopamine to remain in the synaptic cleft for extended periods of time. The longer the dopamine remains in the synaptic cleft the greater its effect. After repeated exposure to drugs of abuse the body's reward center becomes accustomed to the effects. The tolerance developed as a result of adaptation to excessive exposure requires increased dosages in subsequent uses to achieve the same level of euphoria. However, after prolonged drug use addiction can no longer be described solely as the desire for the increased positive reinforcement of the drug and the anticipation of the euphoria it produces. Instead, in the face of prolonged use an actual physical dependence occurs, thereby changing the level of addiction. Once physically dependent, the drug abuser faces a psychological addiction impeding his or her cessation of the drug, however, he/she cannot simply quit due to the negative and often severe physical effects of withdrawal (4). Withdrawal from drugs such as opiates can include symptoms such as fever, night sweats, nausea, vomiting, headaches, leg cramps, abdominal pain, and visual changes among other debilitating complaints (3). The body of the addict adapts its normal functions to include the addition of these drugs.

The same adaptations occur in infants exposed to drugs of abuse in utero, proving addiction can occur completely separately from psychological aspects. These babies, born completely addicted to the drugs their mothers expose them to, play no role in asking for the substances or perpetuating drug abuse by seeking additional doses of the drug or drugs. In the case of neonates, behaviors or behavioral adaptations to drug seeking cannot occur prior to birth proving a completely separate physical facet of addiction. Neonatal abstinence syndrome, the neonatal form of adult withdrawal, presents in a high proportion of infants exposed to opiates or other drugs of abuse during a mother's pregnancy (5). A second example for the proof of a completely physical addiction can be seen in pediatric intensive care patients or even adults receiving opiates for pain management or sedation. Following surgery adults often receive potent narcotics to manage postoperative pain, and sometimes require prolonged administration due to surgical complications. Many patients in these situations develop a physical dependence on the narcotics yet do not display the drug seeking and drug abuse often stereotyped as addiction.

Children in pediatric intensive care units receive sedation while on a ventilator to avoid frightening or stressing such a young patient. Doctors administer a combination of drugs, including benzodiazepines and narcotics, to maintain a sufficient level of sedation. Both of these drugs possess high potential for causing physical dependence following repeated exposure. Children spending extensive amounts of time on a ventilator typically require a slow and controlled weaning plan to prevent the adverse effects of withdrawal. Patients suffering from complex congenital heart disease and/or respiratory failure most often receive the combination of these drugs for sedation and pain management, thereby making them very susceptible to opioid and benzodiazepine withdrawal. In recent studies researchers tested the use of standardized weaning plans for dealing with this type of withdrawal through slow tapers. Interestingly, this study shows that patients given fentanyl, a type of narcotic, display a higher occurrence of withdrawal symptoms (2). Their withdrawal does represent a form of addiction; however, these patients receive the drugs without consent and therefore suffer only a physical dependence due to their bodies' adaptations to function with the narcotics and benzodiazepines in their systems.

The number of pregnancies in drug addicted women, particularly those addicted to opioids has risen over the past 30 years (5), thereby raising the number of infants addicted to drugs and suffering from neonatal abstinence syndrome at birth. Nationwide, women of childbearing age (ages 15-39) make up 22% of individuals who abuse drugs, and 91% of these women abuse heroine or other opiates (6). Opiate abuse causes the most severe fetal effects as well as producing the strongest cases of neonatal abstinence syndrome (1). Not only does drug abuse while pregnant produce drug addicted babies it can also cause adverse effects such as intrauterine growth retardation, reduced birth weight and head circumference, prematurity, and an increased rate of neonatal death or sudden infant death syndrome (SIDS) (6). Once born, the babies' bodies do not know how to function without the chemical effects of the drugs producing profound neurological disturbances. This withdrawal manifests as central nervous and gastrointestinal abnormalities, causing high pitched crying, poor sleeping, tremors, increased muscle tone, vomiting, diarrhea, poor weight gain (5), fever, apnea, frantic sucking, and poor feeding in the addicted neonate (1). Recent studies, showing that administration of therapeutic doses of opiates such as phenobarbital reduces the severity of neonatal abstinence syndrome and shortens the amount of hospitalization required for severely addicted neonates, attribute the previously mentioned symptoms to the effects of withdrawal from drugs of abuse (5).

Babies born addicted to narcotics or other drugs of abuse provide an excellent example for a purely physical addiction to narcotics. The same proof can be seen in patients receiving sedation in pediatric intensive care units, because the children receive narcotics without drug seeking behavior and require weaning after repeated exposure. In both instances addiction manifests physically rather than psychologically, proving that an individual does not need to be the stereotype "addict" with behaviors of drug seeking and abuse to be considered addicted to drugs. In the case of some individuals addicted to controlled substances the physical changes in the brain due to unregulated physical addiction can lead to observable behavioral changes; thereby perpetuating dependence through drug abuse and drug seeking behavior. Based upon this evidence, someone suffering from drug addiction does not necessarily represent an individual with a psychological "weakness" that should be overcome. Instead a complex mixture of physical and psychological dependence must be dealt with to overcome an addiction.

References

1)Emedicince, Belik, Jaques MD. "Neonatal Abstinence Syndrome."

2)Franck, LS., Naughton, I, and Winter, I. "Opioid and benzodiazepine withdrawal symptoms in paediatric intensive care patients." Intensive Critical Care Nursing 20 (2004): 344-51.

3)Emedicine, Jain, Ashok MD. "Withdrawal Syndrome."

4)Kandel, Eric R., Schwartz, James H. and Thomas M. Jessell, ed. Principles of Neural Science. New York: McGraw –Hill, 2000.

5)Langenfeld, Stefan et al. "Therapy of the neonatal abstinence syndrome with tincture of opium or morphine drops." Drug and Alcohol Dependence 77 (2005): 31-36. Science Direct. 6 May 2005.

6)McElhatton, P.R. "Fetal Effects of Substances of Abuse." Journal of Toxicology 38 (2000): 194. InfoTrac OneFile Plus. 6 May 2005.

7)Nestler, Eric J. "Molecular mechanisms of drug addiction." Neuropharmacology 47 (2004): 24-32. Science Direct. 6 May 2005.

8)Robinson, Terry E., Kolb, Bryan. "Structural plasticity associated with exposure to drugs of abuse." Neuropharmacology 47 (2004): 33-46.


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