Source Paper
The Circuitry Mediating Cocaine-Induced Reinstatement of Drug-Seeking Behavior
Krista McFarland, Peter W. Kalivas
Journal of Neuroscience • 2001
Cocaine-Induced Reinstatement Testing
Objective: Evaluate the role of limbic-striato-pallidal circuitry in cocaine-induced reinstatement of drug-seeking behavior by transiently inhibiting specific brain nuclei
Gather these items before starting the experiment. Check off items as you prepare.
Equipment1
Not explicitly stated • Not explicitly stated • Not explicitly stated • Not explicitly stated
Materials3
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Protocol Steps
Baseline drug self-administration training
Subjects trained to self-administer cocaine (details not explicitly provided in text)
Note: Prerequisite for reinstatement testing
View evidence from paper
“cocaine-induced reinstatement of drug-seeking behavior”
Transient inhibition of VTA
Transiently inhibit the ventral tegmental area and test for cocaine-induced reinstatement
Note: VTA inhibition prevented cocaine-induced reinstatement
View evidence from paper
“The transient inhibition of brain nuclei associated with motor systems [including the ventral tegmental area (VTA)]”
Transient inhibition of dPFC
Transiently inhibit the dorsal prefrontal cortex and test for cocaine-induced reinstatement
Note: dPFC inhibition prevented cocaine-induced reinstatement
View evidence from paper
“The transient inhibition of brain nuclei associated with motor systems [including the dorsal prefrontal cortex (dPFC)]”
Transient inhibition of NAcore
Transiently inhibit the core of the nucleus accumbens and test for cocaine-induced reinstatement
Note: NAcore inhibition prevented cocaine-induced reinstatement
View evidence from paper
“The transient inhibition of brain nuclei associated with motor systems [including the core of the nucleus accumbens (NAcore)]”
Transient inhibition of VP
Transiently inhibit the ventral pallidum and test for cocaine-induced reinstatement
Note: VP inhibition prevented cocaine-induced reinstatement and was necessary for food reinstatement
View evidence from paper
“The transient inhibition of brain nuclei associated with motor systems [including the ventral pallidum (VP)]”
Simultaneous bilateral microinjection of GABA agonists
Perform simultaneous unilateral microinjection of GABA agonists into dPFC in one hemisphere and VP in contralateral hemisphere
Note: This manipulation abolished cocaine reinstatement, supporting series circuit hypothesis
View evidence from paper
“simultaneous unilateral microinjection of GABA agonists into the dPFC in one hemisphere and into the VP in the contralateral hemisphere abolished cocaine reinstatement”
Dopamine receptor blockade in dPFC
Block dopamine receptors only in the dPFC and test for cocaine-induced reinstatement
Note: Dopamine receptor blockade in dPFC antagonized cocaine-induced reinstatement
View evidence from paper
“the blockade of dopamine receptors only in the dPFC antagonized cocaine-induced reinstatement”
Dopamine administration to dPFC
Administer dopamine directly into the dPFC and test for reinstatement of drug-related responding
Note: DA administration into dPFC was sufficient to elicit reinstatement
View evidence from paper
“DA administration into the dPFC was sufficient to elicit a reinstatement in drug-related responding”
Food reinstatement control test
Test whether VP inhibition is necessary for food-induced reinstatement
Note: Only VP proved necessary for food reinstatement, suggesting circuit specificity to drug-related reinstatement
View evidence from paper
“only the VP proved to be necessary for food reinstatement, suggesting that the identified circuit is specific to drug-related reinstatement”