Conditioned Place Preference Extinction
Overview
CPP extinction measures the decay of conditioned drug-context associations through repeated non-reinforced exposure to both compartments. After standard CPP has been established, the subject undergoes daily free-access sessions without any drug administration until the preference score returns to baseline. This process engages infralimbic prefrontal cortex (IL-PFC) projections to the nucleus accumbens shell that promote new inhibitory learning rather than erasing the original drug-context association. Understanding extinction mechanisms is central to developing relapse prevention strategies.
The extinction rate is quantified by tracking the CPP score across successive sessions and fitting an exponential decay function to determine the half-life of preference decline. The number of sessions to criterion (CPP score within a predefined threshold of zero) serves as the primary endpoint. Persistent preference despite extended extinction suggests extinction resistance, a phenotype associated with heightened relapse vulnerability. Transition counts and locomotor activity across sessions help distinguish motivational changes from general behavioral suppression.
ConductMaze supports multi-day extinction protocols with automated session scheduling and preference tracking across the full time course. The software computes running CPP scores after each session, plots extinction curves in real time, and applies user-defined criterion thresholds to flag extinction completion. Between-session consistency metrics and within-session time-bin analyses reveal the temporal dynamics of preference decay. All extinction data integrate seamlessly with prior conditioning and subsequent reinstatement phases.
Trial Flow
CPP Verification
Confirm CPP expression with an initial post-conditioning preference test.
Extinction Session
Subject explores both compartments with free access; no drug administered.
Preference Assessment
Calculate CPP score for the current extinction session.
Criterion Check
Compare CPP score to extinction criterion; continue or advance to reinstatement.
Repeat Sessions
Continue daily extinction sessions until criterion is met across consecutive sessions.
Data Export
Export extinction curve, sessions-to-criterion, and per-session preference data.
Phase Complete
Clean apparatus; subject proceeds to reinstatement testing or study conclusion.
Parameters
| Parameter | Type | Default | Description |
|---|---|---|---|
| Extinction Session Duration | duration | 20 min | Duration of each drug-free free-access extinction session. |
| Maximum Extinction Sessions | integer | 14 | Maximum number of daily extinction sessions before study termination. |
| Extinction Criterion Threshold | seconds | 30 | Maximum CPP score magnitude to qualify as extinguished. |
| Consecutive Criterion Sessions | integer | 2 | Number of consecutive sessions below threshold required for extinction criterion. |
| Inter-Session Interval | duration | 24 hr | Time between consecutive extinction sessions. |
| Door Open Delay | seconds | 5 | Delay after placement before compartment doors open. |
Metrics
| Metric | Unit | Description |
|---|---|---|
| Sessions to Extinction | count | Number of sessions required to meet the extinction criterion. |
| CPP Score per Session | s | Preference score for the drug-paired side at each extinction session. |
| Extinction Rate | s/session | Slope of the extinction curve across sessions. |
| Final CPP Score | s | CPP score at the last extinction session. |
| Compartment Transitions | count | Number of between-compartment crossings per session. |
| Distance Traveled | cm | Total locomotion per extinction session. |
Sample Data
| Subject | Group | Sessions to Extinction | Initial CPP (s) | Final CPP (s) | Transitions (last) |
|---|
Representative data for illustration purposes. Actual values will vary by species, strain, and experimental conditions.
Applications
- 1Extinction Pharmacology — Test whether NMDA receptor agonists (D-cycloserine) or HDAC inhibitors accelerate CPP extinction as potential relapse prevention adjuncts.
- 2Infralimbic Cortex Function — Evaluate IL-PFC contributions to extinction learning using targeted lesions or optogenetic silencing during extinction sessions.
- 3Individual Vulnerability — Identify extinction-resistant phenotypes that predict higher reinstatement susceptibility in subsequent relapse tests.
- 4Sex Differences in Extinction — Compare extinction rates between sexes to model gender differences in addiction recovery trajectories.
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