Associative
Tolerance
Lesson 14
Heterogenic Conditioned
Drug Responses

Insulin = US
Hypoglycemia = UR
 CS = peppermint odor
 CS alone measure CR = ?
 Hyperglycemia!
 Opponent processes
 Also role in associative tolerance ~

Heterogenic Conditioned
Drug Responses
Conditional
Stimulus
odor
US
Insulin
UR
hypoglycemia
hyperglycemia
Conditional
Response
Learning & Drug Tolerance
Shepard Siegel (1975)
 Associative Drug Tolerance
 Classically Conditioned Response
 Opponent process theory ~

Overall response:
Opponent Process Theory
Typical drug effects
 function of time
 Physiological disturbance
 A process
 Compensatory response
 B process
 Back to baseline
 set point ~

Overall response
Hi
A process + B process
set point
euphoria
Lo
Time
Drug Effects &
Compensatory Response
Hi
A process = UR
baseline
euphoria
B process
Lo
Time
Observed Response
A process = UR
 homeostatic disturbance
 Observed Response = A + B processes
 Net effects
 Environmental cues become CS
 injection ~

Associative Tolerance
Compensatory response becomes
conditioned
 Starts sooner
 more efficient
 Present CS only  B process only
 CR is opposite to UR ~

Conditioning: Associative Tolerance
Hi
A process = UR
euphoria
baseline
B process
Lo
Time
Conditioning: Associative Tolerance
Hi
A process = UR
euphoria
baseline
B process
Lo
Time
Conditioning: Associative Tolerance
Hi
A process = UR
euphoria
baseline
B process
Lo
Time
Conditioning: Associative Tolerance
Hi
A process = UR
euphoria
baseline
B process
Lo
Time
Paradoxical Opiate Overdose
Death from respiratory depression
 lower than usual dose?
 Siegel (1975)
 Associative tolerance ~

Associative Tolerance
Give rats morphine in white box
 depresses respiration
 repeated morphine  tolerance
  drug   respiration
 Opponent process
 compensatory response
 B process = increased respiration ~

Phase 1
Tolerance

Test
Group 1
Group 2
Test
 Group 1  hi dose in white box
same effects on respiration
 Group 2  hi dose in black box
death ~
“Overdose” death
Why?
 No Conditioned response (CR)
 No CS (white box)
 Same as getting much larger dose ~

Opponent Process Theory
Potential Explanation For...
CR opposite to UR
 Heterogenic CR
 Tolerance
 Paradoxical Heroin OD
 Conditioned drug withdrawal
 craving & drug seeking
 relapse ~

Classical Conditioning...
CR similar to UR
 Homogenic CR
 *Sensitization
 Context-dependent
 Placebo Effects
 LSD Flashback
 Acquisition of Drug Paraphernalia
 “Needle Freaks” ~
