Drug Tolerance, Withdraw, Sensitization and Dependence

8/10/2019 Drug Tolerance, Withdraw, Sensitization and Dependence

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Drug Tolerance, Withdraw,

Sensitization and Dependence


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Drug Tolerance

Mithradates, 63 B.C., tries to commit suicide by

poisoning himself

He had been defeated by the Roman general Pompey and

his son led a successful revolt against him

The attempt fails

Why?

Out of fear of being poisoned to death, he had beeningesting increasing amounts of poison until he could

toleratethem without ill effects

Drug tolerance


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Drug Tolerance

Decreased effectiveness (potency) of a drugthat results from repeated administration

The necessity of increasing the dose of adrug in order to maintain its effectiveness

Not all effects of a drug show tolerance at the

same rate, or at all Develop tolerance to effectsof drugs, not to

the drugs themselves


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Mechanisms of Tolerance

Metabolic Tolerance

Increase in the rate at which the bodymetabolizes and eliminates a drug

Usually enzymatic

Will diminish all drug effects


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Physiological Tolerance Bodys response to drugs controlled by

homeostaticmechanisms

Processes initiated to maintain a set point

Adjustments made by the body to compensate forthe effects of the continued presence of a drug

May include entire systems particular to a singledrug effect (e.g., increased body temperature)

Or at the level of a single cell (e.g., increasing ordecreasing the number of receptors, or altering

the amount of neurotransmitter release)


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Tolerance will develop in a circumstance

where a drug places demand on anorganisms homeostatic mechanism

Tolerance to drug effects that are not

detected or that do not disrupt functioning

does not develop


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Behavioral Tolerance

Learned or conditioned tolerance throughexperience with a drug


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Behavioral Tolerance based on

Classical Conditioning

Classical Conditioning An animal (including people) learnto produce

reflexive responses to previously neutral stimuli i.e., stimuli that initially produce no observable response

Learning = a relatively permanent change inbehavior as the result of experience

If a neutral stimulus (in the past caused noresponse) is paired with a stimulus that reflexivelycauses a response, the neutral stimulus will cometo cause a similar response


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The Terminology

Unconditioned (al) Stimulus (US)

It is the biologically significant event thatreflexively causes a response

Unconditioned Response (UR)

The reflexive response to the US


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The Start of conditioning

The US produces a UR but CS produces

nothing US (meat powder)

CS (tone)

Response

(salivation)

TIME


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Test trails

Present the CS ONLY on an occasional trialintermixed among reinforced (CS-US) trials

If CS alone produces a response, it is a CR

Learning (conditioning) is measured as the strengthof the CR

Or as the percentage of test trials on which a CR occurs What would happen if you presented a blockof CS

only trials?


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Extinction trials

Present the CS only for a BLOCK of trials

No CS-US pairings occur during the block What will happen to the CR?

It will dissipate


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Typical Findings

010

20

30

40

50

60

70

80

acq acq acq acq ext ext ext ext

training

CRs

trength

Line 1Spontaneous Recovery

Asymptote


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More phenomenon

Subject makes a CR tostimuli similar in some wayto the CS

Only one CS has ever beendirectly paired with the US (itis the CS+)

All others are CS-

Strength of CR is a function

of similarity to original CS+

Called StimulusGeneralization

0

20

40

60

CS- CS+ CS-similarity to CS+

%CR


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More phenomenon

With repeated exposureto CS+ (always paired

with US) and CS-(never paired with US)the subject learns todiscriminate betweenthe two

Stimulus Discrimination

0

10

20

30

40

50

60

70

80

CS- CS+

%CR


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Pavlov

s Cerebral Conditioning

Theory

Pavlovs is a contiguity theory

Contiguous=next or near in time or sequence a US and CS need only be contiguous for

conditioning (learning) to occur

It is also a stimulus substitution view

i.e, the CR is a weakly activated UR


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The Nature of the CR Is it just a weak UR?

US UR CR

Bright light Pupil constriction same

food Salivationsame

shock Muscle contractionsame

Air puff eyeblinksame

shock Increase HR Decrease HR


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The Nature of the CR

If mimicking the UR would be adaptive, theCR will be the same

If mimicking the UR would be maladaptive,the CR will be opposite

Consider morphine

US = drug UR = analgesia (reduced sensitivity to pain) or

euphoria


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Opponent Process Theory

0

20

40

60

80

100120

140

160

180

1 2 3 4

UR

OP


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Opponent Process Theory

Now suppose there is a stimulus that reliably

predicts the US

A CS? What might some of these be for morphine or

heroin?

What happens if the CS is presented without the

US?

Drug tolerance, overdose, craving, withdraw

What about diet coke?


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Operant Conditioning

Not all behaviors are reflexive in nature

Some are ACTS ON THE ENVIRONMENT These behaviors also change with

experience

i.e., learning


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B.F. Skinner

There are 2 types of responses and therefore 2

types of learning

Operant behavior

Emitted responses

Operant = interaction with the environment in order to obtain

reinforcement

Learning associated with operants is Type R learning Operant Conditioning


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B.F. Skinner

DV = response rate, or operant strength

Reinforcement affects operant strength Learning = changes in operant strength


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B.F. Skinner

Skinner attempted to identify environmental

factors that influenced operant strength

Response rate

LEARNING


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Classifying Reinforcers

Primary Things that are naturally reinforcing (no learning or

conditioning required) Innate, biological significance

Food, water, shelter, sex

Secondary Acquire reinforcing properties only through learning

(conditioning) Not initially reinforcing themselves

Money, tokens, stars


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Classifying Reinforcers

Positive Causes an increase in operant strength when it occurs

Increases the probability of a response that precedes it Negative

Causes an increase in operant strength when it is removed

Increases the probability of a response that precedes itremoval

As a model of drug taking Drugs are self-administered because they act as reinforcers


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Attempts to Decrease Operant Strength

Punishment Causes a decrease in operant strength when it occurs

Decreases the probability of a response that precedes it Omission Training

Causes a decrease in operant strength when it is removed

Decreases the probability of a response that precedes itsremoval


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Dependence and addiction

Addiction The addicted individual has impaired control over the use of

the drug The drug use has harmful consequences

Addiction as physical dependence Dependence

Discontinuation of the drug causes withdraw symptoms, or

A person compulsively takes a drug These are not the same

Physical vs Psychological dependence

Homeostatic theory vs reinforcement theory

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Drug Tolerance, Withdraw, Sensitization and Dependence