Reinstatement
Overview
The reinstatement model is the most widely used preclinical paradigm for studying relapse to drug seeking. After self-administration training and extinction, drug-seeking behavior is reinstated by one of three triggers: (1) a drug-priming injection (drug-primed reinstatement), (2) re-exposure to drug-paired cues such as the cue light (cue-induced reinstatement), or (3) a stressor such as foot shock or yohimbine injection (stress-induced reinstatement). Each trigger activates distinct neural circuits.
Drug-primed reinstatement depends on ventral tegmental area dopamine projections to the nucleus accumbens and prefrontal cortex. Cue-induced reinstatement engages basolateral amygdala-to-nucleus accumbens pathways. Stress-induced reinstatement involves corticotropin-releasing factor (CRF) signaling and noradrenergic circuits. This dissociation makes the reinstatement model invaluable for developing targeted anti-relapse medications.
ConductMaze automates the complete reinstatement procedure: self-administration acquisition, extinction with daily criterion tracking, and reinstatement testing with automated drug priming (via syringe pump), cue presentation, or foot shock delivery. The software manages multi-phase protocols spanning weeks and generates phase-specific analysis including within-session time course of reinstated responding.
Trial Flow
Self-Admin Phase
Drug self-administration training to stable baseline
Extinction Phase
Daily extinction sessions until criterion met
Extinction Criterion
Active presses < 25% of SA baseline for 2 consecutive days?
Reinstatement Trigger
Drug prime, cue presentation, or stressor delivered
Test Session
Responses recorded in extinction conditions
Comparison
Reinstated responding vs. extinction baseline
Data Output
Phase comparison and reinstatement magnitude calculated
Parameters
| Parameter | Type | Default | Description |
|---|---|---|---|
| Reinstatement Type | enum | Cue-Induced | Trigger modality (drug-primed, cue-induced, stress-induced, context-induced) |
| Priming Dose | float | 10.0 | Drug dose for drug-primed reinstatement (mg/kg, IP) |
| Shock Intensity | float | 0.5 | Foot shock intensity for stress-induced reinstatement (mA) |
| Cue Duration | seconds | 5 | Duration of conditioned cue presentation |
| Test Session Duration | seconds | 7200 | Duration of reinstatement test session |
| Extinction Criterion | integer | 25 | Percent of baseline below which extinction is considered complete |
| Min Extinction Sessions | integer | 7 | Minimum number of extinction sessions before reinstatement test |
| Active Lever Side | enum | Right | Which lever was drug-associated during self-administration |
Metrics
| Metric | Unit | Description |
|---|---|---|
| Reinstated Active Presses | count | Active lever presses during reinstatement test |
| Extinction Baseline Presses | count | Mean active presses during last 2 extinction sessions |
| Reinstatement Magnitude | ratio | Test presses / extinction baseline presses |
| Inactive Presses | count | Inactive lever presses during test (motor control) |
| Latency to First Press | seconds | Time from trigger delivery to first active press |
| Time Course (30-min bins) | presses/bin | Active presses in successive 30-minute bins during test |
Sample Data
| Phase | Active_Presses | Inactive_Presses | Infusions_or_NA | Session_Duration_min | Magnitude |
|---|
Representative data for illustration purposes. Actual values will vary by species, strain, and experimental conditions.
Applications
- 1Relapse prevention — testing anti-relapse medications against specific reinstatement triggers
- 2Neural circuitry — dissecting drug-primed vs. cue vs. stress pathways with targeted manipulations
- 3Sex differences in relapse — comparing reinstatement magnitude between male and female animals
- 4Contextual relapse — context-induced reinstatement (ABA renewal) for environmental trigger studies
- 5Pharmacotherapy development — FDA-recognized preclinical model for anti-craving drug screening
Related Protocols
Compatible Products
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