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 Self-Administration
Objective: Assess the relative contributions of glutamate and dopamine within the nucleus accumbens to cocaine-induced reinstatement of drug-seeking behavior through lever pressing in operant chambers
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Protocol Steps
Cocaine self-administration training
Animals trained to self-administer cocaine through lever pressing in operant chambers
Note: Training phase to establish drug-seeking behavior
View evidence from paper
“Animals were trained to self-administer cocaine through lever pressing in an operant chamber”
Extinction of cocaine self-administration
Cocaine self-administration behavior was extinguished prior to reinstatement testing
Note: Extinction phase to eliminate active drug-seeking before testing reinstatement
View evidence from paper
“When extinguished cocaine self-administration behavior was reinstated by a cocaine-priming injection”
Cocaine-priming injection and reinstatement testing
Cocaine-priming injection administered to reinstate extinguished lever-pressing behavior; extracellular dopamine and glutamate levels measured in nucleus accumbens
Note: Cocaine self-administration group showed elevated dopamine and glutamate; yoked cocaine and saline controls showed only dopamine elevation
View evidence from paper
“When extinguished cocaine self-administration behavior was reinstated by a cocaine-priming injection, extracellular levels of both dopamine and glutamate were elevated in the nucleus accumbens”
Lever withdrawal condition
Levers withdrawn from operant chamber during cocaine-priming injection to test whether glutamate elevation depends on lever-pressing behavior
Note: Cocaine self-administration group still demonstrated elevated glutamate even without levers available
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“the cocaine self-administration group still demonstrated elevated glutamate when the levers were withdrawn from the operant chamber”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
Reinstatement of lever pressing for food reinforcement tested to determine if glutamate elevation is specific to drug reinforcement
Note: Food reinforcement did not elevate extracellular glutamate, indicating glutamate increase is selective for drug reinforcement
View evidence from paper
“reinstatement of lever pressing for food did not elevate extracellular glutamate, indicating that increased glutamate initiated responding selectively for a drug reinforcement”
Prefrontal cortex glutamatergic inhibition
Prefrontal cortical glutamatergic neurons projecting to nucleus accumbens inhibited to test source of glutamate
Note: Inhibiting prefrontal glutamatergic neurons 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”
