Siegel, 1976

Demonstration of addiction, tolerance and withdrawal or

Cues are EVERYWHERE!

Defining Addiction

• remember it’s the 1970’s– DSM II going into DSM III– addiction = psychological process

• Define tolerance and addiction– addiction = psychological need (at this point)– tolerance:

• decreasing effectiveness of drug• requiring increasing amounts to get same effect• become dependent on drug

– withdrawal: • physiological symptoms which occur with withdrawal of drug• suggests dependence

Do Animals Show “Addiction”?

• Most animals will not begin drugs on their own– have to “preload”– initial response to drugs such as morphine = decreased

responding– then increase in responding to gain access

• do show tolerance and withdrawal– once addicted, process is same– symptoms overlap as well– thus: indicates must be physiological in nature, not just

“psychological”

Opiate Tolerance:

• Emphasizes associative characteristics of drug administrative procedure– shows that it is the associative pairing that may be critical– notes that tolerance is maintained over long time periods,

and even after ECS

• Show several characteristics– retention of tolerance is long and strong– metabolic intervention changes parameters of tolerance– retardation of consolidation of tolerance when add memory

disruptors as learning (e.g. ECS, etc.)

Opponent processes in classical conditioning

• Drug Tolerance Research:– drug tolerance = decrease in effectiveness of a drug with

repeated usage– many theories as to why occurs- e.g.- opponent process

theory

• Seigel (1975): proposed is due to classical conditioning:

• used morphine (analgesic)• decrease in analgesia over successive morphine injections

controlled by contextual stimuli

Original study: Rats and hot plate

• Rats given injections of morphine across several stimulus trials:– first three trials-

• kept context cues identical• got decreasing analgesia

– 4th trial- • changed location of injections to home cage-• got increase in analgesic effects

• why: context cues acquired capacity to elicit compensatory CR's of hyperalgesia; when changed context, these cues were gone

Siegel: CR not equal UR!

• Difficult to predict form of the CR:– may be identical to very similar– may be opposite– Compensatory responses: compensate for or

counteract the UR

• Literature review at the time supported this.

Opponent Process:

• Time curve analysis of these responses:• opponent

processes• for every action

there is a reaction!

Can Predict Response?• Figure A: drug not yet associated with predrug

environmental cues; drug effect not yet modulated by any anticipatory responding

• Figure B: – as effect of drug increases and decays following

administration, increasing frequency of drug and environmental context pairing

– drug administration not only followed by pharmacological UCR, but also by drug compensatory CR

– net drug effect is smaller than initial because drug UR is attenuated by compensatory CR

Can Predict Response?• Figure C: – Interaction between drug UR and preparatory CR

after many trials– CR is large, net result of interaction between this

CR and direct drug effect is very small– Note: Biphasic: paradoxical conditioning or

opposite conditioning effect!– Can actually become HYPERSENSITIVE to effects at

higher dosage!– This is how you die!

• So: what are withdrawal symptoms?

Learning Effects?

• Physical Effects:– body again rebounding– expecting something- but not happening– step down reflex: Alpha and Beta Receptors– if go on long enough: Marilyn Monroe

• Notice: Learning effects:– needle begins to be CS for heroin– but notice: opposite effect (process B) to the needle– stimuli can become conditioned to the "emotion"

What stimuli can serve as cues?

• ANY environmental cue predicting drug

• tolerance occurs because of context of environmental cues that predict drug

• in sense, tolerance is a learning effect, not a true drug effect

• what are cues?– Environmental– Physical– Psychological

What stimuli can serve as cues?• Environmental cues:– the place setting: room, lighting, sounds, etc.– the experimenter– time of day– olfactory cues

• Physical effects of the drug – state of body– initial effects

What stimuli can serve as cues?• signaled vs. unsignaled cues: –much stronger conditioning to signaled cues –more predictive!

• can develop discriminative control of tolerance– show in some settings, not in others– can have VARIED response to same drug,

and dose!

How can we retard tolerance?

• CS habituation

• Partial reinforcement of tolerance:– Different strengths of street drugs– not all CSs followed by US/same US– dilute CS-US relationship

• extinction of tolerance

The Expectancy Effect

• expect effects dependent on environmental cues

• thus, show compensatory responses when “expect” drug

• these are simply withdrawal effects

look at responses compared in table 6.2 on page 157

Humans react the same!

What does this mean for applied setting?

• Must pay attention to environmental cues• both intentional cues• and unintentional cues

• remember that this learning is VERY robust!• May be stronger than you think• even smallest cues, if reinforced, can maintain the behavior• explains why relapse is so common and prevalent• also explains why so difficult to treat:

• detox and treatment centers vs real world

• what happens when put individuals back into their original setting?

Real World Situations

• Vietnam drug addiction experience– Not show when got home– Why?

• animals can show strong relapse as well

• inadvertent cues SO powerful

• bottom line: conditioning occurs EVERYWHERE!