chap 12 - drug abuse Flashcards

Question

cerebellum

Answer 1

sites which support self-stimulation - deep cerebellar nuclei

Answer 2

sites which support self-stimulation - motor nucleus of trigeminal nerve - nucleus of tractus solitarius

Answer 3

- one of the "hottest" brain pathways for self-stimulation - when it is electrically stimulated, axons of dopaminergic neurons are indirectly stimulated by way of the ventral tegmental area -The "indirection" hypothesis to account for electrical self-stimulation of the brain: effects of medial forebrain bundle stimulation. When the medial forebrain bundle is electrically stimulated, axons of dopaminergic neurons are indirectly stimulated by way of the ventral tegmental area. MFB, medial forebrain bundle.

Answer 4

Drugs that facilitate self-stimulation release CAs (e.g., amphetamine). Drugs that inhibit self-stimulation deplete CAs (reserpine, -methyl-p- tyrosine). Drugs that block adrenergic transmission (chlorpromazine) inhibit self-stimulation. Protection of CAs with monoamine oxidase inhibitors or block reuptake (e.g., imipramine) enhances the facilitatory effect of amphetamine on self-stimulation. Depletion of brain CAs with reserpine or -methyl-p-tyrosine decreasesthe facilitatory effects of amphetamine on self-stimulation. A large component of the medial forebrain bundle (MFB), a “hot-spot” for self-stimulation, is catecholaminergic. Rewarding stimulation of the MFB causes release of norepinephrine intothe amygdala and hypothalamus.

Answer 5

– Horizontal projections of the ascending DA and NA pathways. Terminal fields in the cortex are not shown. - Catecholaminergic neuronal pathways in the rat brain. Upper: Noradrenergic neuronal pathways. Lower: Dopaminergic neuronal pathways. AC, nucleus accumbens; ACC, anterior cingulate cortex; CC, corpus callosum; FC, frontal cortex; HC, hippocampus; HY, hypothalamus; LC, locus coeruleus; ME, median eminence; MFC, median forebrain bundle; OT, olfactory tubercle; SM, stria medullaris; SN, substantia nigra; ST, striatum.

Answer 6

nigrostriatal, mesolimbic, mesocrotical

Answer 7

In vivo microdialysis was used to assess extracellular DA levels in the nucleus accumbens of rats during intracranial self-stimulation of the ventral tegmental area. Dopamine levels were monitored before, during, and after 15 min bouts of stimulation at three different current intensities (18-27 A). Increasing current intensity led to enhanced rates of self-stimulation (right ordinate) and elevated DA concentrations in the nucleus accumbens.

Answer 8

- electrode stimulates MFB - DA neuron in ventral tegmental area - infusion of DA-R blocker decreases slef stimulation

Answer 9

Two-compartment apparatus for assessing conditioned place preferences produced by psychoactive drugs in rats. One compartment has a grid floor and checkered walls; the other compartment has a smooth floor and grey walls. During conditioning sessions, rats are allowed access to only one compartment at a time; one compartment is repeatedly paired with drug injections and the other compartment with vehicle injections. During test sessions, rats have access to the whole apparatus and the amounts of time spent in each compartment are recorded by a system of light beams and photocells.

Answer 10

This experiment showed that micro-infusions of dopamine agonists directly into the nucleus accumbens caused place preference for the side of the cage associated with the infusion. Two different dopamine agonists were used. The control infusions were isotonic saline. The results are interpreted as indicating that the rats liked the experience of DA in the nucleus accumbens by preferring the side in which they received the infusion. Details: Rats were given twelve daily place conditioning sessions in an apparatus with two compartments that differed in their sensory properties. On 6 alternating days, each animal was given an intra-accumbens infusion of a DA agonist (the D1 receptor agonist SKF 38393 or the D2 agonist quinpirole) and then sequestered for 30 min in one of the compartments. On the other 6 days, a saline control infusion was administered, and the animal was sequestered in the other compartment. On the test day, the animal was given free access to both compartments, and the time spent in each was measured during a 20 min test session. The drug-paired side was significantly preferred for all doses of SKF 38393 and for all, but the highest dose of quinpirole.

Answer 11

This is a demonstration that administration of a highly rewarding drug (cocaine) causes release of dopamine into the nucleus accumbens. - Rats were implanted with microdialysis probes in the nucleus accumbens. The next day, extracellular dopamine concentrations were measured in the freely moving animals following intraperitoneal injection of either 0.5 mg/kg THC, 1.0 mg/kg THC, or vehicle. Asterisks denote a statistically significant difference from the vehicle condition (*P<0.05; ** P<0.01).

Answer 12

This is a demonstration that administration of a highly rewarding drug (cocaine) causes release of dopamine into the nucleus accumbens and that the release of DA can be classically conditioned.. The first injection produces a modest increase and the last, after 7 days, produces a much greater increase in dopamine release. Note that whereas the first saline injection produces no effect on dopamine levels, the second, given 3 days after 7 days of cocaine injections, produces a significant rise in dopamine, presumably due to conditioning.

Answer 13

Another way to assess the reward value of a drug is with self-administration studies. The willingness of an animal to self-administer a drug is a sign that the animal likes the effects that the drug produces. Self-administration shows that the drug is a reinforcer. Willingness to self-administer a drug is also a major factor in determining if a drug has addiction potential. A drug MUST support self-administration in order to be considered addictive.

Answer 14

It turns out that nicotine has a narrow dose range at which it produces self-administration in animals. For that reason, academic scientists had not shown that it was a reinforcer because none had stumbled upon the correct dose range. However, the tobacco company scientists had demonstrated nicotine self-administration in rats and had kept the information to themselves while the company leaders lied on TV to congress about having any evidence of nicotine’s addictive ability.

Answer 15

Drugs that support self-administration and electrical self-administration can act at different points in the reward pathways. Some drugs act in the VTA to stimulate DA neurons while others act at the DA synapse in the n. accumbens. - Intracranial self-stimulation may act directly on descending myelinated fibers. Suspected sites of drug actions are shown in boxes. Acc = nucleus accumbens; DA = dopaminergic fibers; Enk – enkephalin and other opioid-containing neurons; GABA = GABAergic inhibitory interneurons; LC = locus coeruleus; NE = norepinephrine-containing fibers; THC = tetrahydrocannabinol; VTA = ventral tegmental area.

Answer 16

All of the currently known drugs that possess dependence liability are known to enhance dopamine (DA) activity in the n. accumbens as depicted in this figure. These drugs increase DA through several different mechanisms. Through the afferent and efferent connections of the n. accumbens, this region can readily control the development of contingent reward, leading to "drug craving." This craving is thought to occur independent of the other effects of these drugs such as the withdrawal syndrome, tolerance, and euphoria.

Answer 17

One Involves Cognitive Processes and the Other Involves Those in Response to Basic Motivations (Drives) and Emotions -Activation of reward pathways also initiates movements and behaviors associated with obtaining the rewarding stimulus. Thus, there is an interaction between neural pathways that provide a sense of reward and pathways which initiate motor movement. This is a schematic of two systems responsible for the initiation of movements: one involves cognitive processes and the other involves responding to basic motivations (drives) and emotions and includes the VTA  nucleus accumbens pathway. Both systems use output from the globus pallidus to initiate movement.

Answer 18

part of the basal ganglia

Answer 19

Locomotion Occurs When Inhibitory GABA-Secreting Synapses on Neurons in the Medial Globus Pallidus Decrease Their Activity

Answer 20

"translates" the perception of a reward into locomotion - The circuitry mediating the perception of reward and the initiation of adaptive behavioral responding to reward. The nucleus accumbens is viewed as a primary anatomical locus for integrating GABAergic, glutamatergic and dopaminergic input, and the ventral pallidum is viewed as the primary output nucleus communicating with classic motor systems.

Answer 21

1) Occasional, controlled social use 2) Drug abuse or harmful use 3) Drug addiction or substance dependence categorized according to frequency, situation, context, and consequences

Answer 22

Drug abuse is a maladaptive pattern of substance use manifested by recurrent and significant adverse consequences to repeated use of substances.

Answer 23

A. A maladaptive 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: * Recurrent substance use resulting in a failure to fulfill major role obligations at work, school, or home (e.g., repeated absences or poor work performance related to substance use; substance-related absences, suspensions, or expulsions from school; neglect of children or household). * Recurrent substance use in situations in which it is physically hazardous (e.g., driving an automobile or operating a machine when impaired by substance use). * Recurrent substance-related legal problems (e.g., arrests for substance-related disorderly conduct). * Continued substance use despite having persistent or recurrent social or interpersonal problems caused or exacerbated by the effects of the substance (e.g., arguments with spouse about consequences of intoxication, physical fights). B. The symptoms have never met the criteria for Substance Dependence for this class of substances.

Answer 24

Drug dependence (or drug addiction) is a state whereby an individual either psychologically or physically requires a drug in order to feel well in the absence of some medical indication. Characterized by: - Compulsion to seek and take a drug. - Loss of control in limiting intake. - Discontinuation of the drug will produce a characteristic group of withdrawal symptoms. - Physiological dependence – adverse physiological reactions (e.g., stomach cramps) in the absence of drugs. - Emergence of a negative emotional state (e.g., dysphoria, anxiety, irritability) when access is prevented and/or the drug reduces "psychic" discomfort (drug craving).

Answer 25

-- A need for markedly increased amounts of the substance to achieve intoxication or desired effect. -- Markedly diminished effect with continued use of the same amount of the substance.

Answer 26

as manifested by either of the following: -- The characteristic withdrawal syndrome for the substance (refer to Criteria A and B of the criteria sets for withdrawal from the specific substances). -- The same (or a closely related) substance is taken to relieve or avoid withdrawal symptoms.

Answer 27

- The substance is often taken in larger amounts or over a longer period than was intended. - There is a persistent desire or unsuccessful efforts to cut down or control substance use. - A great deal of time is spent in activities necessary to obtain the substance (e.g., visiting multipledoctors or driving long distances), use the substance (e.g., chain-smoking), or recover from its effects. - Important social, occupational, or recreational activities are given up or reduced because of substance use. - The substance use is continued despite knowledge of having a persistent or recurrent physical orpsychological problem that is likely to have been caused or exacerbated by the substance (e.g.,current cocaine use despite recognition of cocaine-induced depression, or continued drinking despite recognition that an ulcer was made worse by alcohol consumption). - Specify if: With Physiological Dependence: evidence of tolerance or withdrawal. Without Physiological Dependence: no evidence of tolerance or withdrawal

Answer 28

- Drugs are likely to be taken in excess when the effects are considered pleasurable. - Legal prescription drugs (e.g., barbiturates, morphine, amphetamine), illegal drugs (e.g., heroin and cocaine) and non-prescription drugs (e.g., ethanol and nicotine) are abused and can produce dependence. - It was once promoted by drug companies and believed that very few individuals begin addiction problems by misuse of prescription drugs. This no longer is true!!! - Prescribed medications for pain, anxiety and even hypertension can produce tolerance and physical dependence. - Tolerance and physical dependence do not necessarily indicate abuse or addiction.

Answer 29

- Physiological and psychological dependence-related symptoms and signs that arise during withdrawal of a drug. - Relationship of abstinence syndrome with the half-life of drug.a constellation of physiologic changes in people or animals who have become physically dependent on a drug or chemical who are abruptly deprived of that substance. Generally, the effects observed are in an opposite direction from those produced by the drug. For example, the withdrawal syndrome from CNS depressants (like barbiturates) consists of insomnia and restlessness. This makes the person want to take the drug again to alleviate the withdrawal symptoms. This is a kind of negative reinforcement situation: the behavioral response of taking the drug removes a negative stimulus—the withdrawal symptoms. The onset of abstinence syndrome depends on the half-life of the drug: the shorter the half-life, the sooner the onset—in a person with some signs of dependence.

Answer 30

As a rule of thumb, the severity or intensity of the withdrawal effects depends on the intensity and duration of the drug effects. If you note, in A there is an intense drug effect, but it is spaced-out, so the intensity is not constant. In B, with more closely-spaced administrations, the intensity is more prolonged until there is tolerance, and this causes some withdrawal response. In C, there is close-spaced administration to maintain the intensity AND more drug is used to counter the effects of tolerance and this produces the greatest withdrawal intensity. Main Point: In case A with a short-acting drug administered at spaced intervals, there is likely to be no pharmacodynamic tolerance and no withdrawal. In case B, in which a short-acting drug is administered at a constant dosage and at closely spaced intervals, there is likely to be pharmacodynamic tolerance and a mild, but short-lasting, abstinence syndrome. In case C, in which the short-acting drug is administered at closely spaced intervals, and the dose is increased (indicated by X), there is likely to be a relatively more intense and longer-lasting abstinence syndrome than in case B. In case D, with a longer-lasting drug administered at spaced intervals, pharmacodynamic tolerance will not be readily apparent, and the abstinence syndrome (if evident at all) will be mild. In case E, in which the longer-lasting drug is administered at more closely spaced intervals, pharmacodynamic tolerance and the abstinence syndrome will be somewhat more apparent than in case D. Furthermore, while the abstinence syndrome in case E may be less severe than in case C, it is likely to be more protracted.

Answer 31

A person who injects heroin several times per day oscillates between being sick and being high. In contrast, the typical methadone patient remains in the "normal" range (indicated in gray) with little fluctuation after dosing once per day. The curves represent the subject's mental and physical state and not plasma levels of the drug.

Answer 32

Stages of addiction to drugs of abuse. Drug-taking invariably begins with social or experimental drug-taking and acute reinforcement and often, but not exclusively, then moves in a pattern of use from escalating compulsive use to dependence, withdrawal, and protracted abstinence. During withdrawal and protracted abstinence, relapse to compulsive use is likely to occur with a repeat of the cycle. Genetic factors, environmental factors, stress, and conditioning all contribute to the vulnerability to enter the cycle of abuse/dependence and relapse within the cycle.

Answer 33

Stages of addiction to drugs of abuse. Drug-taking invariably begins with social or experimental drug-taking and acute reinforcement and often, but not exclusively, then moves in a pattern of use from escalating compulsive use to dependence, withdrawal, and protracted abstinence. During withdrawal and protracted abstinence, relapse to compulsive use is likely to occur with a repeat of the cycle. Genetic factors, environmental factors, stress, and conditioning all contribute to the vulnerability to enter the cycle of abuse/dependence and relapse within the cycle.

Answer 34

Physical Dependence Model: Avoidance (escape) of withdrawal symptoms (Traditional View) Positive reinforcement models (1960s-'70s) Medical disorder/"disease" model Incentive-sensitization (Robinson & Berridge) Counteradaptation: opponent process theory (Koob & Le Moal) Dopamine-induced activation of Fos-related antigens (Fra; Nestler)

Answer 35

the reinforcing properties of a given drug are the reason why people become addicted to the drug in the first place and they crave it for the rewarding properties.

Answer 36

suggests withdrawal sickness/ symptoms are so bad the user takes the drug to avoid the withdrawal symptoms.

Answer 37

suggests that the ‘abnormal behaviors’ are caused by a disease state brought on by drug usage. This model simply labels drug addiction as a disease; which takes the individual out of control of the addictive behavior. It is claimed that the behavior of an addict is not normal behavior because of its compulsive tendencies.

Answer 38

drug addiction develops from a sensitization of the mesolimbic dopamine system from repeated exposure to a drug. - Dopamine normally functions to attribute incentive salience to stimuli associated with rewards (like food and sex) and triggers reward “wanting”. Drugs hijack this “wanting” system. Following repeated use of drugs, the dopamine system becomes hyper-responsive and drug cues become hyper-salient. This means drug cues are nearly impossible for addicts to ignore, and when they are encountered, they can lead to intense cravings and/or relapse. This sensitized cue-triggered drug 'wanting' can persist for years after an addict quits drugs, and long after drug withdrawal has ceased. This fact may account for the tendency of former addicts to relapse to drug use after quitting, sometimes even after many years of abstinence.

Answer 39

says that the drug initially produces pleasurable feelings, but then a negative emotional experience occurs. Eventually, the drug user takes drugs not for their pleasurable effects, but to avoid withdrawal symptoms. - Opponent-process can be seen as an explanation for “learned tolerance”. Recall that drug effects take the body away from homeostasis, so the body makes a counter-response. That is what we can visualize here in part A. After repeated drug use (part B), the body counters the drug response better-and-better so less-and-less drug effect is felt (i.e., tolerance) and, in this case, more-and-more of the negative, or abstinence, withdrawal effects are felt.

Answer 40

Diagram illustrating an extension of Solomon and Corbit's opponent-process model of motivation to incorporate the conceptual framework of components of drug addiction. All panels represent the affective response to the presentation of the stimuli (that is, drug administration). (A) The original description of the affective stimulus, is argued to be a sum of both an a-process and a b-process and represents the initial experience with no prior drug history. (B) The same affective stimulus in an individual with an intermittent history of drug use that may result in sensitized response. The shaded line illustrates the same trace of the initial experience in (A). The upper line represents the sensitized response. (C) Change in the affective stimulus hypothesized to exist in the heavily dependent individual (that is, after chronic exposure) where there is a major change in the hedonic set point. This represents a change sufficient to be considered a major break with hedonic homeostasis. (D) The hypothesized state of protracted abstinence and enhanced vulnerability to relapse with a history of chronic continuous experience. The change in this panel reflects the change in the affective response in an organism with a history of dependence where there is both a change in set point that is long-lasting and a residual sensitization

Answer 41

life cycle of addiction – the complex, time-dependent effects of drug exposure. The upper boxes show the prominent processes associated with each stage of drug action; the lower boxes show the underlying molecular and cellular mechanisms involved. The dashed arrow indicates that the changes in neurotransmission associated with short-term abstinence (withdrawal) are thought to be mediated by the molecular and cellular adaptations associated with the chronic drug state (dependence).

Answer 42

that dependence is due to a consequence of reverse tolerance to dopamine (DA) in the n. accumbens. DA activates cAMP which, in turn, activates protein kinases which carry the signal into the nucleus where long-lasting alterations in transcription are thought to occur. Acting through cAMP response element binding protein (CREB), an acute, nuclear response can occur, whereas during chronic treatment, Fos-like proteins have been shown to activate Fra proteins that can lead to reverse tolerance and drug sensitization.

Answer 43

- Will vary with the drug being used and social and cultural factors determining the use - The management of withdrawal syndromes can be achieved with minimal risk and high probability of success using pharmacological agents - Key issues in treatment are detoxification and maintaining abstinence

Answer 44

Most patients will perceive withdrawal symptoms. May be possible to reduce the amount of the drug. Methadone is suitable for suppressing withdrawal symptoms. With methadone substitution in an in-patient setting, symptoms usually aren't worse than "flu-like" syndrome. Under these "drug weaning" conditions, most patients can be withdrawn in less than 10 days. Clonidine (2-adrenergic receptor agonist) can suppress some components of opioid withdrawal. Clonidine suppresses autonomic signs and symptoms (e.g., nausea, vomiting, diarrhea) then drug craving.

Answer 45

anxiety, sweating, fast heart rate, shakiness, vomiting, mild fever

Answer 46

seizures, hallucinations (auditory, visual), delirium tremens

Answer 47

- Abrupt neurodepressant withdrawal can be fatal. - Pentobarbital can be substituted for any neurodepressant. - Pentobarbital is administered to induce mild intoxication and maintained 24 to 36 hrs and stabilized, then withdrawal can be started.

Answer 48

- Therapeutics may be used to treat underlying psychological problem (e.g., anxiety or depression). - Therapeutic agents intended to be a less toxic substitute (e.g., methadone) may be used. - Drugs to interfere with reinforcing actions of the abused drug (e.g., naltrexone).

Answer 49

Most consistent pharmacotherapy has been obtained with tricyclic antidepressants (e.g., desipramine). After 1 to 2 weeks, desipramine appears to reduce craving for cocaine. It is postulated that the antidepressants increase functional activity in reward systems by altering cocaine-induced supersensitivity at dopamine autoreceptors.

Answer 50

depression. Depression-like symptoms during cocaine withdrawal include slowed activity, reduced physical and mental energy, unpleasant dreams, changes in appetite, and a general feeling of discomfort. Some people may also experience anhedonia, or the inability to feel pleasure. There is also some evidence that desipramine specifically alleviates cravings and compulsions associated with cocaine abuse. Although this mechanism is not well understood, altering cocaine-induced supersensitivity at dopamine autoreceptors is certainly possible.

Answer 51

used In the pharmacotherapy of opioid addiction. It is a partial opioid agonist and can be thought of as occupying a midpoint between opioid full agonists (e.g., methadone, LAAM) and opioid antagonists (e.g., naltrexone, nalmefene). It has sufficient agonist properties such that individuals addicted to opioids perceive a reinforcing subjective effect from the medication, often described in terms of “feeling normal.

Answer 52

is a naturally occurring psychoactive substance found in plants in the family Apocynaceae. It is a psychedelic with dissociative properties. Preliminary research indicates that it may help counter drug addiction

Answer 53

- is a medication used along with counselling to treat alcohol use disorder. Acamprosate is thought to stabilize chemical signaling in the brain that would otherwise be disrupted by alcohol withdrawal

Answer 54

opioid and alcohol dependency

Answer 55

alcohol dependency

Answer 56

opioid dependency

Answer 57

opioid dependency

Answer 58

opioid dependency

Answer 59

patches and gum

Answer 60

Little evidence that traditional individual psychotherapy is of value for compulsive drug user. Cognitive or expressive psychotherapy has improved poor prognosis patients in methadone programs. Special forms of group therapy and self-help groups have been demonstrated to reduce relapse.

Answer 61

Alcoholic anonymous, narcotics anonymous, Phoenix House, etc.

Answer 62

Abstinence during a period in a hospital, prison, or special facility followed by supervision in the community.

Answer 63

alpha-2-adrenergic receptor agonist - can suppress some components of opiod withdrawal

Answer 64

suitable for suppressing withdrawal symptoms

Answer 65

around 6 hours following the last drink and are worst at 24-72 hours and improve by 7 days