1. Associative Tolerance Lesson 14

2. n Insulin = US l Hypoglycemia = UR l CS = peppermint odor n CS alone measure CR = ? l Hyperglycemia! n Opponent processes l Also role in associative tolerance ~ Heterogenic Conditioned Drug Responses

3. odor Conditional Stimulus Insulinhypoglycemia USUR hyperglycemia Conditional Response Heterogenic Conditioned Drug Responses

4. Learning & Drug Tolerance n Shepard Siegel (1975) n Associative Drug Tolerance l Classically Conditioned Response l Opponent process theory ~

5. Overall response: Opponent Process Theory n Typical drug effects l function of time n Physiological disturbance l A process n Compensatory response l B process n Back to baseline l set point ~

6. Overall response Hi Lo set point euphoria Time A process + B process

7. Hi Lo baseline Time Drug Effects & Compensatory Response euphoria A process = UR B process

8. Observed Response n A process = UR l homeostatic disturbance n Observed Response = A + B processes l Net effects n Environmental cues become CS l injection ~

9. Associative Tolerance n Compensatory response becomes conditioned l Starts sooner l more efficient n Present CS only  B process only n CR is opposite to UR ~

10. Hi Lo baseline euphoria Time A process = UR B process Conditioning: Associative Tolerance

11. Hi Lo baseline euphoria Time A process = UR B process Conditioning: Associative Tolerance

12. Hi Lo baseline euphoria Time A process = UR B process Conditioning: Associative Tolerance

13. Hi Lo baseline euphoria Time A process = UR B process

14. Paradoxical Opiate Overdose n Death from respiratory depression l lower than usual dose? n Siegel (1975) n Associative tolerance ~

15. Associative Tolerance n Give rats morphine in white box l depresses respiration l repeated morphine  tolerance l  drug   respiration n Opponent process l compensatory response l B process = increased respiration ~

16. n Test l Group 1  hi dose in white box same effects on respiration l Group 2  hi dose in black box death ~ Phase 1 Tolerance Test Group 1 Group 2

17. “Overdose” death n Why? n No Conditioned response (CR) l No CS (white box) n Same as getting much larger dose ~

18. Opponent Process Theory Potential Explanation For... n CR opposite to UR l Heterogenic CR n Tolerance n Paradoxical Heroin OD n Conditioned drug withdrawal l craving & drug seeking l relapse ~

19. Classical Conditioning... n CR similar to UR l Homogenic CR n *Sensitization l Context-dependent n Placebo Effects n LSD Flashback n Acquisition of Drug Paraphernalia n “Needle Freaks” ~