Source Paper
Prefrontal Glutamate Release into the Core of the Nucleus Accumbens Mediates Cocaine-Induced Reinstatement of Drug-Seeking Behavior
Krista McFarland, Christopher C. Lapish, Peter W. Kalivas
Journal of Neuroscience • 2003
Cocaine-Primed Reinstatement Test
Objective: To assess the relative contributions of glutamate and dopamine within the nucleus accumbens to cocaine-induced reinstatement of drug-seeking behavior by measuring extracellular neurotransmitter levels when extinguished cocaine self-administration behavior is reinstated by a cocaine-priming injection
This is a Cocaine-Primed Reinstatement Test protocol using Not explicitly stated in provided text as the model organism. The procedure involves 7 procedural steps, 3 equipment items, 2 materials. Extracted from a 2003 paper published in Journal of Neuroscience.
Model and subjects
Not explicitly stated in provided text • Not explicitly stated in provided text • unknown • Not explicitly stated in provided text • Not explicitly stated in provided text
Study window
Estimated timing pending
Core workflow
Cocaine self-administration training • Extinction training • Cocaine-priming injection
Primary readouts
- Extracellular dopamine levels in nucleus accumbens
- Extracellular glutamate levels in nucleus accumbens
- Lever pressing behavior during reinstatement
- Comparison of neurotransmitter levels between cocaine self-administration group, yoked cocaine controls, and saline controls
Key equipment and reagents
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Protocol Steps
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Cocaine self-administration training
Animals were trained to self-administer cocaine through lever pressing in operant chambers
Note: This is the acquisition phase prior to extinction
View evidence from paper
“cocaine self-administration behavior was reinstated by a cocaine-priming injection”
Extinction training
Cocaine self-administration behavior was extinguished through repeated sessions without drug delivery
Note: Animals learned that lever pressing no longer resulted in cocaine delivery
View evidence from paper
“When extinguished cocaine self-administration behavior was reinstated”
Cocaine-priming injection
A cocaine-priming injection was administered to reinstate drug-seeking behavior in extinguished animals
Note: Administered to cocaine self-administration group, yoked cocaine controls, and saline controls
View evidence from paper
“When extinguished cocaine self-administration behavior was reinstated by a cocaine-priming injection”
Measurement of neurotransmitter levels
Extracellular levels of dopamine and glutamate were measured in the nucleus accumbens during reinstatement
Note: Measurements were taken during lever pressing reinstatement and when levers were withdrawn
View evidence from paper
“extracellular levels of both dopamine and glutamate were elevated in the nucleus accumbens”
Lever withdrawal test
Levers were withdrawn from the operant chamber while measuring neurotransmitter levels to assess if glutamate elevation was dependent on the motor act of lever pressing
Note: Cocaine self-administration group still demonstrated elevated glutamate when levers were withdrawn
View evidence from paper
“the cocaine self-administration group still demonstrated elevated glutamate when the levers were withdrawn from the operant chamber”
Food reinforcement control test
Reinstatement of lever pressing for food was tested to determine if glutamate elevation was specific to drug reinforcement
Note: Food reinforcement did not elevate extracellular glutamate, indicating selectivity for drug reinforcement
View evidence from paper
“reinstatement of lever pressing for food did not elevate extracellular glutamate”
Prefrontal cortex inhibition manipulation
Prefrontal cortical glutamatergic neurons projecting to the accumbens were inhibited to determine the source of glutamate
Note: Inhibition prevented the rise in glutamate during cocaine-primed reinstatement
View evidence from paper
“inhibiting prefrontal cortical glutamatergic neurons that project to the accumbens prevented the rise in glutamate”