Conditioned Place Preference Reinstatement

Overview

CPP reinstatement models relapse by testing whether a drug priming injection, stress exposure, or conditioned cue can restore an extinguished place preference. After CPP is established and subsequently extinguished, the subject receives a triggering stimulus (typically a sub-threshold drug dose, footshock stress, or drug-associated cue) immediately before a free-access test session. Reinstatement is mediated by distinct but overlapping circuits: drug priming activates VTA-NAc dopamine projections, stress reinstates via corticotropin-releasing factor in the bed nucleus of the stria terminalis, and cue reinstatement involves basolateral amygdala-to-prefrontal pathways.

The reinstatement score is the difference between the reinstated CPP score and the final extinction CPP score, with a positive value indicating restoration of preference. The magnitude of reinstatement relative to the original CPP score indicates the proportion of the drug memory that was reactivated. Transition counts during reinstatement help differentiate approach-motivated reinstatement from anxiety-driven side avoidance. Locomotor activity confirms that reinstatement reflects specific motivational changes rather than generalized behavioral activation from the priming stimulus.

ConductMaze integrates the full CPP acquisition-extinction-reinstatement workflow in a single protocol timeline, maintaining continuous subject tracking across phases. The system automatically computes reinstatement indices referenced to both extinction baseline and original CPP magnitude. The platform supports multiple reinstatement trigger types with configurable pre-session intervals for drug pharmacokinetics. Time-bin analysis within the reinstatement session reveals whether preference is immediate or emerges over time.

Trial Flow

start

Extinction Verification

Confirm CPP has been extinguished by verifying preference score is at criterion.

input

Reinstatement Trigger

Administer priming stimulus (drug injection, stress, or cue presentation).

process

Absorption Interval

Wait for drug onset or stress response before placing subject in apparatus.

input

Reinstatement Test

Subject explores all compartments with free access; record dwell times.

decision

Reinstatement Assessment

Compare reinstatement CPP score to extinction baseline and original CPP magnitude.

output

Data Export

Export reinstatement indices, time-bin preference data, and full longitudinal CPP trajectory.

end

Protocol Complete

Clean apparatus; archive complete acquisition-extinction-reinstatement dataset.

Parameters

ParameterTypeDefaultDescription
Reinstatement Test Durationduration20 minDuration of the post-priming free-access reinstatement test.
Priming Stimulus TypeenumdrugType of reinstatement trigger: drug priming, stress, or conditioned cue.
Drug-Test Intervalduration15 minDelay between drug priming injection and reinstatement test start.
Stress Durationduration10 minDuration of stress exposure (footshock or restraint) if stress reinstatement.
Priming Dose Fractionfloat0.25Fraction of original conditioning dose used for drug priming (e.g., 0.25 = quarter dose).
Time Bin Sizeduration5 minDuration of time bins for within-session preference analysis.
Door Open Delayseconds5Delay after subject placement before doors open.

Metrics

MetricUnitDescription
Reinstatement ScoresReinstatement CPP score minus extinction baseline CPP score.
Reinstatement CPP ScoresPreference for the drug-paired side during the reinstatement test.
Reinstatement RatioratioReinstatement score divided by original CPP score, indicating proportion of memory reactivated.
Drug Side TimesAbsolute time in drug-paired compartment during reinstatement.
Compartment TransitionscountNumber of between-compartment crossings during reinstatement.
Distance TraveledcmTotal locomotion during the reinstatement session.

Sample Data

SubjectGroupExtinction CPP (s)Reinstatement CPP (s)Reinstatement Score (s)Transitions

Representative data for illustration purposes. Actual values will vary by species, strain, and experimental conditions.

Applications

  • 1
    Relapse Prevention PharmacologyScreen anti-relapse compounds by measuring their ability to block drug-primed reinstatement of CPP.
  • 2
    Stress-Induced RelapseModel stress-triggered drug seeking using footshock or restraint stress as the reinstatement stimulus.
  • 3
    Memory ReconsolidationTest whether post-reactivation anisomycin or propranolol disrupts reconsolidation and prevents subsequent reinstatement.
  • 4
    Circuit-Specific Relapse MechanismsUse pathway-specific chemogenetics to identify which projections are necessary for cue versus drug versus stress reinstatement.

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