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General Arousal and Tolerance, Drug Abuse, & Habitual Behavi

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Xavier Orellana

on 23 October 2013

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Transcript of General Arousal and Tolerance, Drug Abuse, & Habitual Behavi

BRODEUR & DUBOIS
tolerance can be brought about by change in sensitivity of relevant system to the drug or transmitter
their experiment called for daily administration of drugs to rats
after 60 days, tolerance developed
previous effects of the drug weren't observed

REASONS FOR THE TOLERANCE
change in the sensitivity of the postsynaptic membrane
can occur through neuromodulation (neuron uses several neurotransmitters to regulate diverse populations of neurons in central nervous system)
these changes in receptor populations involve some major commitments of cellular metabolism
Changes in Receptor Sensitivity
WHAT IS IT?
tachyphylaxis literally means "rapid protection"
result of rapid emptying of transmitter substance from synaptic vesicles
tolerance that develops to the effects of indirect acting drugs
can be intercepted by time course & other drugs
doesn't represent permanent change
Tachyphylaxis
General Arousal and Tolerance
&
Drug Abuse and Habitual Behaviors

General Arousal
Drugs That Decrease Arousal
Drugs That Change Perception
The drugs that generally do this are centrally active drugs. These drugs often are the hallucinogenics, psychedelic, mind altering, etc., that essentially change the way you view things while intoxicated. It is thought that these are taken voluntarily as an escape their perception of anxiety. An example given is a non-intoxicated person can go stand next to a church and look up imagining it is spiraling up into the sky. If they were to nurture this thought it could be considered that they are having a religious experience.
LSD, Scopolomine, Angel Dust

General Arousal
Drugs That Increase Arousal
Behaviour
Foundations of Abuse
Strychnine, Picrotoxin and Pentylenetetrazol
Strychnine
Extremely potent drug that causes general excitation of the central nervous system, especially the reflexes of the spinal cord.
Used in more traditional medicine and used in some street formulas to add a stimulating effect to a variety of different drugs.
Played an important role in research. It help unravel some of the mechanisms of brain and spinal cord circuits. High dosages of strychnine produce an exaggeration of spinal reflexes that can result in tonic seizures within the limbs
Picrotoxin
Derived from the seeds of the fishberry shrub
Stimulates nervous system activity by blocking inhibition
Pentulenetetrazol
A synthetic drug
Does not interfere with any particular transmitter, but reduces the recovery time following action potentials.
Used as a seizure inducing drug in the process of screening drugs that may have anticonvulsant activities.
The Xanthine Derivatives
The most widely used stimulants and they appear to be safe in moderate dosages
The most common and most potent of these is caffeine, with theophylline being somewhat less effective, and theobromine being considerably less effective.
These substances are found in coffee, cocoa, tea and cola in different amounts
They are not linked to any specific transmitter rather they increase calcium permeability
Effects include a decrease in fatigue and drowsiness, an increase in speed and efficiency, and a decrease in the number of errors
Nicotine
A powerful stimulant that is most commonly administered by smoking tobacco
Produces a bewildering array of influences, most of which occur by virtue of its ability to mimic acetylcholine at certain receptor sites
Could trigger cardiac failure in certain individuals
Nicotine also acts on skeletal muscle receptors, but the initial stimulation phase is either very short lived or nonexistent.
The overall effect is a relaxation of muscles at low or moderate dosages and paralysis at higher dosages.
Nicotine also influences neurons throughout the central nervous system
Sympathomimetics
Increase the activity of neurotransmitters associated with the sympathetic nervous system, namely, norepinephrine and dopamine
The most widely used drugs within this class include the amphetamines and cocaine.
Amphetamines
Have a variety of different effects on neurons that release catecholamines, including the ability to directly mimic the neurotransmitters at the receptor site
Major role appear to be the indirect release of newly synthesized dopamine
The symptoms include an increase in the startle response, twitching, and related dyskinesias that may be due to a reduction of dopamine in the caudate.
Cocaine
Present in the leaves of a shrub that grows high in the Andean mountains of South America
Produces a numbing sensation because of its local anesthetic actions
Cocaine acts on the same neuronal systems as amphetamine, but enhances the effects of catecholamines by blocking reuptake
The organism is more responsive to the environment, and the rewarding effects of that environment are amplified
General Arousal
Moruzzi and Magoun's experiment (1949) on arousal was very helpful because they discovered the reticular formation in the brain. This area is in charge of the somnolence of a patient. They found that if they used transection on the spinal cord, they had little to no reaction as compared to when they used it higher up, they found that the somnolence was more permanent. Yerkes- Dodsen Law (1908) states that "an organism interacts most efficiantly with its environment when the level of stimulation is at some intermediate level" anything lower wouldn't be enough stimulation.
Benzodiazepines and Barbiturates
Alcohol
Anticholinergic Drugs
reduce the activity of excitable tissues
benzodiazepines are more effective toward reducing anxiety
barbiturates are more effective as being anesthetics
both have been used to treat sleep disorders
have sedative effects- make it easier to fall asleep, increase sleeping time
sleep is less effective than normal
sleep deprived
Terminology
Self Administration
Reinforcement Restructured
Environmental Bridges
Breaking the Cycle
intake can lead to the inflammation of tissues, especially the membranes
can kill cells
can reduce peripheral nerves to conduct impulses=> giving some anesthetic properties
but not medically useful since the dosages may be lethal
can lead to coma or death
can result in an exaggeration of spinal reflexes and the appearance of behaviors
physiological changes: increase of adrenal hormones, lactic acid and fatty acids are released into blood stream, heart rate increases, decrease in hormones that increase urine outflow
slower absorption
ultimately metabolized to produce energy
undesirable side effects such as dry mouth, pupil dilation with blurred vision, and rapid heartbeat
hypnotic or sedative effects
when tested on animals, it appears the animals to be slow and sleepy (lack of voluntary attention to environment), yet they were still behaviorally awake
The terms “drug addiction” and “drug abuse” seemed to work well when describing certain cases of drug use but it became more and more difficult to accurately describe certain instances.
For example: Tobacco use involves craving, but the degree of dependence (i.e., physiological need) is much less dramatic than in the case of morphine or barbiturates.
A distinction has sometimes been made between a drug habit and a drug addiction to reflect the differing physiological bases that control the use of the drug.
The distinction is equally blurry when one tries to draw the lines between moderate drinking, heavy drinking, and alcohol addiction.
If an individual's use of a drug is extensive enough to interfere with work, family, or lifestyle, then the drug is being abused.
Researchers now speak of substance abuse because there is a growing recognition that behavior itself can be the object of abuse like gambling or overeating.
psychological dependence is not necessary for addiction though it can be a large contributor.
This is most easily seen in laboratory models of addiction in which animals are given the opportunity to self administer drugs.
there is a fairly close correspondence between the list of drugs that are abused by humans and the list of drugs that animals will self administer in the laboratory.
The drugs that can be used as reinforcers appear to have three characteristics in common:
They act on the CNS.
The CNS effects occur rapidly.
After continued use, withdrawal results in rebound effects.

The behavior of a rat in a self administration experiment shows many parallels to drug use in humans.
For example, in the case of morphine, the initial rate of which the rat presses the lever to obtain the drug may be very low. Gradually, over a period of days and weeks, tolerance to the morphine begins to develop and the lever pressing shows correspondingly greater rates in order to inject the greater amount of drug that is required to produce the "desired" effects.
The drug not only acts as a reinforcer, but sets the stage for the development of the motivation to obtain the drug.
Not all drugs that have abuse potential show close parallels between human usage and laboratory models.
It is almost embarrassingly difficult to get laboratory animals to consume alcohol.
Brain Mechanism of Arousal
Moruzzi and Magoun's (1949) description of the reticular formation helped us understand the midbrain .
They proposed that the reticular formation was a sort of general "power supply" to determine the level of activity of the entire brain.
This was called reticular activating system
The idea that a brain area was responsible for arousal led us to believe that the brain area could be directly responsible for putting an animal to sleep.
Transection at the level of the spinal cord had little or no effect on arousal.
Transection at a somewhat higher level resulted in permanent wakefulness
Transection at a still higher level led to permanent somnolence
Mechanisms of Tolerance
WHAT ARE ENZYMES?
protein molecules that increase speed of chemical reactions
high affinity for particular chemical structures
ineffective for body to produce and store all enzymes
enzyme induction limits production to only necessary enzymes

EFFECT ON METABOLISM OF DRUGS
involves protein synthesis which takes several hours
e.g. first injection of drugs may induce formation of an enzyme, but undergo very slow metabolism
may stay in system for a very long period of time
Enzyme Induction
IT'S KIND OF LIKE HOMEOSTASIS
various types of tolerance are an extension of homeostasis
b/c organism reacts by attempting to return system back to normal
has important consequences of effectiveness and rebound changes once it's gone

IN NICOTINE & CAFFEINE
the more you do it, the harder it will be to quit
b/c tolerance balanced out effects of the drug, therefore deeming it difficult to quit
rebound effect: sleepiness, lack of energy, etc. that comes after trying to quit
Behavioral Tolerance
Sleep, Arousal, and Environmental Change
Circadian Rhythms
The circadian rhythm it provides a constantly changing environment in which drugs must act.
Changes in hormone levels, body temperature, rate of metabolism, heart rate, blood pressure, gastrointestinal activity, sleep cycles and behavioral activity levels.
Drugs will have differing effects for a given dosage.
Higher doses are required during the active periods, increasing the risk of overdose
Drugs that specifically alter any of these physiological systems have the potential to disrupt the normal rhythmicity and cause secondary problems.
Arousal as Reward
One of the earliest and most influential statements about this relationship is the Yerkes-Dodsen Law (1908).
Below this level, the organism misses features from the environment.
Above this level will result in exaggerated responses to all elements and a decrement in performance.
Arousal as Reward (Continue)
Behavior is also an important way to achieve a change in arousal.
Butler (1958) and Tapp (1969) conducted test to prove this.
Are all behaviors that cannot be explained by the traditional motivators of hunger, thirst, or reproduction.
Hull (1952) and Spence (1956.) drive theory believe that the test had to do with curiosity:
Had two effects: (a) an energizing effect that increases the general behavior of the organism, and (b) a directing effect that channels the behavior toward relevant goal objects.
When reinforcement is obtained, the drive and its resulting energy is reduced.
When extinction or nonreinforcement in encountered, the energy is intensified and the behavior is less channeled.

a drug that requires an environmental bridge in the laboratory gains such control over so many people in the natural environment because the route of administration is ideal in terms of the speed of the effect. The inhalation of nicotine in tobacco smoke produces very rapid effects, reaching the brain within 8 seconds.
John Carpenter unveiled the phenomenon that has come to be known as the Think-Drink effect. The subject either received alcohol or not and were told that they were receiving alcohol or not.The behavioral measures (including social aggressiveness, talkativeness, motor coordination, and others) showed that the behavior was more closely related to what the participants thought they were drinking than to what they actually were drinking.

There is no clear formulation that can guarantee success in the attempt to break drug abuse patterns, but several suggestions can be made, based upon the way in which the abuse pattern has been established and maintained.

1. Change the US (Unconditioned Stimulus) effects of the drug
break the cycle of smoking by chewing gum with nicotine
2. Change the reward structure
forced smoking, rapidly smoking one cigarette after the other
3. Change the environmental cues
change ones schedule or furniture set up like moving the T.V. to another room
4. Avoid using the drug
Environmental Bridges Continued
One of the most interesting set of findings is that there are some subcultures that use a fairly large amount of alcohol, but have very low incidences of abuse. Children are exposed to alcohol at an early age as part of the meal instead of seeing it as a symbol of adulthood. This cultural difference reduces alcohol abuse in the future.
METHODS TO INCREASE DRUG TOLERANCE
reduce chances of reaching receptors
launch biological counterattack against effects of drug

WAYS TO REDUCE CHANGES
lowering rate of absorption from stomach and intestines
increasing the rate at which the drug is being eliminated
increasing binding of drug molecules w/ other larger molecules to halt movement

BIOLOGICAL COUNTERATTACK
increase activity of an opposing system

SO BASICALLY...
the body's response to constant drug administration changes
also, changes in one system may affect future responses to other drugs
General Tolerance
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