chap 12 - drug abuse Flashcards
classes of abused substances
- neuro depressants, sedative-hypnotics, anxiolytics
- psychomotor stimulants
- opioids
- hallucinogens
- marijuana
- inhalants
sedative-hypnotics
Most sedatives produce similar psychological effects. First there is a sense of relaxation and a reduction of anxiety – a general “mellow” feeling. At higher doses, this is followed by lightheadedness, vertigo, drowsiness, slurred speech, and muscle incoordination. Learning and memory are impaired.
ethanol
When drinking alcohol, there is a feeling of pleasure and relaxation during the first half-hour or so. People become talkative and socially outgoing, but these feelings are usually replacedby sedation (drowsiness) as the alcohol iseliminated from the body, so drinkers may become quiet and withdrawn later. This pattern often motivates them to drink more in order to keep the initial pleasant buzz going.
Common Names: Liquor, whiskey, booze, hooch, wine, beer, ale, porter.
cocaine and amphetamine
Stimulants are aptly named: These drugs cause a sense of energy, alertness, talkativeness, and well-being that users find pleasurable. At the same time, the user experiences signs of sympathetic nervous system stimulation, including increased heart rate and blood pressure and dilation of the bronchioles (breathing tubes) in the lungs. These drugs also cause a stimulation of purposeful movement that is the reason for their description as psychomotor stimulants. When injected or smoked, these drugs cause an intense feeling of euphoria. With prolonged and high-dose use, the locomotor activity often becomes focused in repetitive movements.
Street Names: Coke, blow, candy, crack, jack, jimmy, rock, nose candy, whitecoat (cocaine); crank, bennies, uppers (amphetamine); meth, crystal, crystal meth, ice (meth- amphetamine); Ritalin (methylphenidate); cat khat, crank, goob (methcathinone)
nicotine
Nicotine is a specific kind of stimulant that increases attention, concentration, and (possibly) memory. Many people also report that nicotine has calming or anti-anxiety effects.
Forms: Tobacco, nicotine chewing gum (Nicorette), nicotine skin patch (Nicoderm), chewing tobacco, snuff, cigarettes, cigars, pipe tobacco, vaping.
caffeine
At low to moderate doses, many people report increased alertness and ability to concentrate, and even euphoria. Higher doses can result in nervousness and agitation.
opiates
Injecting opiates produces a rush of pleasure, then a sinking into a dreamy, pleasant state in which there is little sensitivity to pain. Breathing slows, and skin may flush. Pinpoint pupils are another hallmark of opiate effects. Opiates taken by ways other than injection have the same effect, except that a pleasant drowsiness replaces the rush. Nausea and vomiting can accompany these effects, as well as constipation.
hallucinogens
Experiences vary from individual to individual and from time to time for a single individual. The experience is strongly shaped by the user’s previousdrug experience one’s expectations, and the setting in which he/she takes the drug. Mild effect produced by low doses can include feelings of detachment from the surroundings, emotional swings, and an altered sense of space and time. With higher doses, visual disturbances and illusions (hallucinations) occur. A hallmark of the hallucinogen experience is a sensation of separation from one’s body. Some users experience intense feelings of insight with mystical or religious significance. These effects can last for minutes (with DMT) or for hours (with LSD).
marijuana
Subjective experiences vary widely with
marijuana and depend upon the potency
of the drug taken. In general, smoking
marijuana first relaxes a person and
elevated his/her mood. These effects are
followed about a half-hour later by drowsiness and sedation. Some people experience this as stimulation followed by a relaxed feeling of tranquility. Users may shift between hilarity and contemplative silence, but these swings often reflect the user’s situation. When hashish or high-grade marijuana is eaten, the effects take much longer to be felt (1-2 hrs) and may produce a more hallucinogenic response.
inhalants
All those drugs that are taken by inhalation. The chemicals
in this category have very little in common with each other
(i.e., chemical structure, pharmacology, or toxic effects).
The nitrites relax smooth muscle. Relaxed blood vessels
produce a drop in blood pressure, an increased heart rate, and a sense of
warmth and mild euphoria. Visual distortions can also occur. Nitrous oxide is
by far the mildest of the anesthetics, and it produces mild euphoria, reduction of
pain, and reductions of inhibitions, followed by drowsiness as the concentrations
increase. Other anesthetics produce the same effects, but cause major sedation at
modest levels. Solvents produce effects similar to those of alcohol, with stimulation,
loss of inhibitions, and mild euphoria, followed by depression. Distortions of
perception and hallucinations may occur.
Forms: Nitrites (butyl or amyl); anesthetics (nitrous oxide – Whippets, gaseous
anesthesia agents used for surgery – halothane, ether); solvents, paints,
sprays, and fuels (toluene, gasoline, glues, canned spray paint, etc.).
toleune
inhalant
- can have an intoxicating effect
found in adhesives and solvents
butane
inhalant
- predominant effects can be described as of a hallucinatory and/or a dissociative nature
found in aerosols, and solvents
nitrous oxide
inhalant
- euphoria, numbness of the body, giddiness (laughing gas)
found in anesthetics and canned whip cream
acetone
inhalant
- lightheadedness, giddy, feeling “tingly”
amyl nitrate
- inhalant
pleasurable warmth, intensified sensations, relaxed
theories of self-stimulation
automatistic behavior
Dual activation of drive and reward pathways
Consummatory behavior
Incentive motivation
Hedonic The priming effect in animal research is defined as the enhancement in motivation to obtain a reward, such as food, drugs, or electrical stimulation of the brain (ESB) resulting from pre-exposure to that reward. Therefore, Deutsch and Gallistel contend that BSR activates both motivation and reward pathways.
It may mimic aspects of consummatory behavior (actually acquiring the goal has reinforcement properties)
It may mimic aspect of enhancing the rewarding properties of the goal itself.
i.e.., it is somehow enhancing the natural reward-related properties of the natural motivational systems.
hedonic
the pleasantness of a sensation. Olds believed that ESB simply felt good to the rat.
major neurologic syndromes produced by organic solvents
Encephalopathy
- Central nervous system (e.g., toluene)
- Central and peripheral
- Acute encephalopathy – nonspecific; high level exposure
- Chronic encephalopathy – seen with repeated high-level exposure over years
- Cerebellar ataxia
- Peripheral neuropathy – distal axonopathy
- Cranial neuropathy – primarily cranial nerves V and VII
- Parkinsonism
- Visual loss – optic neuropathy
- Multifocal
drug abuse dependence and addiction
- Behavior is motivated
- Motivation: Drive and Incentive
- Motivation and Reinforcement and Reward
Drive = the need or wanting to obtain the drug
Incentive = the drug is considered a good thing
dependence
is an adaptive state that develops from repeated drug administration, and which results in withdrawal upon cessation of drug use.
Addiction is characterized by compulsive, out-of-control drug use, despite negative consequences (think of smokers who continue smoking after lung removal or with those holes in their throats).
james olds and peter milner
implanted stimulating electrodes into the septal area of the brains of rats.
They observed that rats preferred to return to the region of the open field where they were standing when they received the electrical stimulation. From this demonstration, Olds and Milner inferred that the stimulation was rewarding. They had discovered the reward mechanisms in the brain involved in positive reinforcement. This showed that electrical stimulation could serve as an operant reinforcer. Their discovery enabled motivation and reinforcement to be understood in terms of their underlying physiology, and it led to further experimentation to determine the neural basis of reward and reinforcement. The phenomenon of brain stimulation reinforcement (BSR) has been shown in all species tested including humans.
operant chamber for delivery of rewarding electrical brain stimultion
This phenomenon iquickly came to be studied using rats or other animals lever pressing in order to receive short pulse trains of brain stimulation. Rats will perform lever-pressing at rates of several thousand responses per hour for days in order to obtain direct electrical stimulation of the lateral hypothalamus.
forebrain
sites which support self-stimulationFrontal cortex;
- Entorhinal cortex
- Olfactory nucleus
- Caudate nucleus
- Nucleus accumbens
- Entopeduncular nucleus
-Septal area
- Hippocampus
- Amygdala
- Ventral and medial thalamus
- Hypothalamus
- Median forebrain bundle
- Dorsal noradrenergic bundle
midbrain and brain stem
sites which support self-stimulation
- ventral tegmental area
- substantia nigra
- nucleus coeruleus
- periaqueductal gray matter
- raphe nuclei
- superior cerebellar peduncle
- mesencephalic nucleus of trigeminal nerve
cerebellum
sites which support self-stimulation
- deep cerebellar nuclei
medulla
sites which support self-stimulation
- motor nucleus of trigeminal nerve
- nucleus of tractus solitarius
medial forebrain bundle
- 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.
larry stein - catecholamines mediate rewarding brain stimulation
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.
ascending noradrenaline and dopamine pathways
– 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.
long length brain dopamine systems
nigrostriatal, mesolimbic, mesocrotical
effects of electrical self-stimulation of the ventral tegmental area on extracellular dopamine in the nucleus accumbens
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.
blockade of medial forebrain bundle self-stimulation by dopamine receptor antagonist infused into the nucleus accumbens
- electrode stimulates MFB
- DA neuron in ventral tegmental area
- infusion of DA-R blocker decreases slef stimulation
conditioned place preference
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.
place conditioning with dopamine agonists infused into the nucleus accumbens
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.
thc-induced enhancement of dopamine efflux in the nucleus accumbens
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).
