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
Food Reinforcement Control Test
Objective: Determine if glutamate elevation during reinstatement of drug-seeking behavior is specific to cocaine reinforcement by testing reinstatement of lever pressing for food as a control
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Protocol Steps
Establish cocaine self-administration baseline
Train animals to self-administer cocaine via lever pressing until behavior is established
Note: This establishes the baseline behavior to be extinguished
View evidence from paper
“extinguished cocaine self-administration behavior was reinstated”
Extinction phase
Extinguish cocaine self-administration behavior by removing cocaine reinforcement while maintaining lever access
Note: Animals learn that lever pressing no longer produces cocaine
View evidence from paper
“extinguished cocaine self-administration behavior was reinstated”
Cocaine-priming reinstatement test
Administer a cocaine-priming injection to reinstate lever pressing behavior in extinguished animals
Note: Measure lever pressing reinstatement and concurrent glutamate and dopamine levels
View evidence from paper
“When extinguished cocaine self-administration behavior was reinstated by a cocaine-priming injection”
Food reinforcement control test
Test reinstatement of lever pressing for food reinforcement to determine if glutamate elevation is specific to drug reinforcement
Note: Measure extracellular glutamate levels during food-reinforced lever pressing reinstatement
View evidence from paper
“reinstatement of lever pressing for food did not elevate extracellular glutamate”
Lever withdrawal test
Withdraw levers from operant chamber during cocaine-priming reinstatement to test if glutamate elevation depends on lever pressing behavior
Note: Determine if glutamate increase is due to the act of lever pressing itself
View evidence from paper
“the cocaine self-administration group still demonstrated elevated glutamate when the levers were withdrawn from the operant chamber”
Yoked control administration
Administer cocaine prime to yoked cocaine or saline control subjects who do not perform lever pressing
Note: Compare glutamate and dopamine levels in non-responding animals
View evidence from paper
“when yoked cocaine or saline control subjects were administered a cocaine prime, only dopamine levels were elevated”