Outline

1. Outline Pavlovian/classical conditioning Tolerance Conditioned Tolerance The conditioned-compensatory response model Examples of conditioned tolerance

2. Pavlovian Conditioning An unconditioned stimulus (US) is recurringly paired with a cue and this cue (CS) acquires new response eliciting capacities Training procedure: CS paired with US ? UR Demonstration of conditioning: CS ? CR

3. Tolerance “said to develop when repeated administrations of the drug have progressively less effect.” Classical conditioning plays a role in tolerance Led to the conditioned compensatory-response model (Siegel, 1975) Pg 100-103

4. Definition of Conditioned Tolerance Conditioned tolerance – “is the result of conditioned compensatory responses, developed to environmental stimuli (the conditioned stimulus, CS) accompanying drug administrations (the unconditioned stimulus, US), which attenuate the direct effects of the drug” (Dafters and Anderson, 1982) Hypothesized to be a homeostatic mechanism against drug effects

5. The Compensatory-Response Model Siegel proposed a classical conditioning model of drug tolerance: Initial exposure to drug: CS (initially neutral) US UR Environmental context cues ? drug ? response to drug Subsequent reactions: CS CR Environmental cues ? elicits compensatory response (counters primary response)

6. Testing for conditioned tolerance Typically three groups: (differential conditioning Group 1 – received drug in the context A and placebo in context B Group 2 – received placebo in the context A and drug in context B Group 3 – received placebo in the context A and placebo in context B Test for conditioning: give placebo in context A to all groups; measure compensatory response

7. Previous Research Commonly examined dependent variables Analgesia Lethality Hypothermia

8. Lethality Seigel (1982) Experimental design 3 groups: Group 1 – received heroin in the colony room and placebo in the noisy room Group 2 – received placebo in the colony room and heroin in the noisy room Group 3 – received placebo in the colony room and placebo in the noisy room Tested with heroin after conditioning in either the colony or the noisy room

10. Lethality (Melchior, 1990) Examined the role of conditioned tolerance in ethanol lethality Gave male Balb/c mice two injections daily for four days of ethanol (3.5 g/kg) or saline in a distinct “cued” environment On the fifth day, the mice were given an injection of ethanol (range from 4.5 to 7.0 g/kg) and tested in either the “cued” environment or a novel “uncued” environment Design had four experimental groups: ethanol/cued, ethanol/uncued, saline/cued, and saline/uncued Animals were measured for lethality on Day 5 (all given ethanol) A higher LD50 means a higher dose in order to produce death

11. Design

12. Analgesia Siegel (1975) Examined the role of conditioned cues on development of tolerance to morphine-induced analgesia

13. Conclusions Appears conditioning plays a major role in the development of tolerance Tolerance may by a homeostatic mechanism that protects the animal or person for the drugs effects Conditioned compensatory responses can be produced in humans to ethanol which supports a Pavlovian conditioning model of tolerance