Source Paper
Limbic and Motor Circuitry Underlying Footshock-Induced Reinstatement of Cocaine-Seeking Behavior
Krista McFarland, Susan B. Davidge, Christopher C. Lapish, Peter W. Kalivas
Journal of Neuroscience • 2004
Source Paper
Krista McFarland, Susan B. Davidge, Christopher C. Lapish, Peter W. Kalivas
Journal of Neuroscience • 2004
The role of limbic, cortical, and striatal circuitry in a footshock reinstatement model of relapse to cocaine seeking was evaluated. Transient inhibition of the central extended amygdala [CEA; including the central nucleus of the amygdala (CN), ventral bed nucleus of the stria terminalis (BNSTv), and nucleus accumbens shell (NAshell)], ventral tegmental area (VTA), and motor circuitry [including the dorsal prefrontal cortex (PFCd), nucleus accumbens core (NAcore), and ventral pallidum (VP)] blocked the ability of footshock stress to reinstate lever pressing previously associated with cocaine delivery. However, inhibition of the basolateral amygdala, mediodorsal nucleus of the thalamus, or the ventral prefrontal cortex had no effect on drug-seeking behavior. These data suggest that footshock stress activates limbic circuitry of the CEA that, via the VTA, activates motor output circuitry responsible for producing lever press responding. Consistent with this notion, the D 1 /D 2 dopamine receptor antagonist fluphenazine blocked footshock-induced reinstatement when infused into the PFCd. Further, inhibition of the NAshell blocked a footshock-induced increase in dopamine within the PFC and concomitantly blocked reinstatement responding. Also supporting the idea of a CEA-VTA-motor circuit in stress-induced reinstatement of cocaine seeking, inactivation of the PFCd was shown to block stress-induced glutamate release within the NAcore while concurrently inhibiting reinstatement responding. Taken together, these data suggest that footshock activates limbic circuitry in the CEA, which in turn activates a VTA dopamine projection to the PFCd. The rise in dopamine within the PFCd initiates reinstatement via a glutamatergic projection to the NAcore.
Objective: Evaluate the role of limbic, cortical, and striatal circuitry in footshock-induced reinstatement of cocaine-seeking behavior using transient inhibition and lever pressing measures
This is a Footshock Reinstatement of Cocaine-Seeking protocol using Not explicitly stated in provided text as the model organism. The procedure involves 10 procedural steps, 4 equipment items, 1 materials. Extracted from a 2004 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 • Transient inhibition of central extended amygdala
Primary readouts
Key equipment and reagents
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Animals are trained to self-administer cocaine by lever pressing in operant conditioning chambers
Note: Establishes baseline lever pressing behavior associated with cocaine delivery
“lever pressing previously associated with cocaine delivery”
Lever pressing is no longer reinforced with cocaine to extinguish the drug-seeking response
Note: Establishes extinction baseline before reinstatement testing
“Not explicitly stated in provided text”
Transient inhibition of the central extended amygdala (CEA), including the central nucleus of the amygdala (CN), ventral bed nucleus of the stria terminalis (BNSTv), and nucleus accumbens shell (NAshell)
Note: This inhibition blocks the ability of footshock stress to reinstate lever pressing
“Transient inhibition of the central extended amygdala [CEA; including the central nucleus of the amygdala (CN), ventral bed nucleus of the stria terminalis (BNSTv), and nucleus accumbens shell (NAshell)] blocked the ability of footshock stress to reinstate lever pressing”
Transient inhibition of the ventral tegmental area (VTA)
Note: VTA inhibition blocks footshock-induced reinstatement of lever pressing
“ventral tegmental area (VTA) blocked the ability of footshock stress to reinstate lever pressing”
Transient inhibition of motor circuitry including the dorsal prefrontal cortex (PFCd), nucleus accumbens core (NAcore), and ventral pallidum (VP)
Note: Motor circuitry inhibition blocks footshock-induced reinstatement
“motor circuitry [including the dorsal prefrontal cortex (PFCd), nucleus accumbens core (NAcore), and ventral pallidum (VP)] blocked the ability of footshock stress to reinstate lever pressing”
Infuse D1/D2 dopamine receptor antagonist fluphenazine into the dorsal prefrontal cortex (PFCd)
Note: Fluphenazine blocks footshock-induced reinstatement when infused into the PFCd
“The D1/D2 dopamine receptor antagonist fluphenazine blocked footshock-induced reinstatement when infused into the PFCd”
Apply footshock stress to animals to induce reinstatement of cocaine-seeking behavior
Note: Footshock activates limbic circuitry in the CEA
“footshock stress activates limbic circuitry of the CEA”
Measure the number of lever presses following footshock stress to quantify reinstatement of cocaine-seeking behavior
Note: Primary outcome measure for reinstatement
“blocked the ability of footshock stress to reinstate lever pressing”
Measure footshock-induced increase in dopamine within the prefrontal cortex (PFC)
Note: Inhibition of NAshell blocks this dopamine increase and concomitantly blocks reinstatement
“inhibition of the NAshell blocked a footshock-induced increase in dopamine within the PFC and concomitantly blocked reinstatement responding”
Measure stress-induced glutamate release within the nucleus accumbens core (NAcore)
Note: Inactivation of PFCd blocks stress-induced glutamate release in NAcore while inhibiting reinstatement
“inactivation of the PFCd was shown to block stress-induced glutamate release within the NAcore while concurrently inhibiting reinstatement responding”
This section explains what the experiment is doing, which readouts matter, what the data artifacts usually look like, and how the analysis should flow from raw capture to reported result.
Evaluate the role of limbic, cortical, and striatal circuitry in footshock-induced reinstatement of cocaine-seeking behavior using transient inhibition and lever pressing measures
Objective
Evaluate the role of limbic, cortical, and striatal circuitry in footshock-induced reinstatement of cocaine-seeking behavior using transient inhibition and lever pressing measures
Subjects
From paperNot explicitly stated in provided text • Not explicitly stated in provided text • unknown • Not explicitly stated in provided text • Not explicitly stated in provided text
Cohort notes
From paperNot explicitly stated in provided text
Cocaine self-administration training (Not explicitly stated)
Extinction training (Not explicitly stated)
Transient inhibition of central extended amygdala (Not explicitly stated)
Transient inhibition of ventral tegmental area (Not explicitly stated)
Lever pressing behavior (reinstatement of cocaine-seeking)
From paperNot explicitly stated in provided text
Artifact type
Endpoint measurements summarized by group or timepoint
Comparison focus
Compare endpoint magnitude between groups, timepoints, or both
Dopamine levels in prefrontal cortex
From paperNot explicitly stated in provided text
Artifact type
Endpoint measurements summarized by group or timepoint
Comparison focus
Compare endpoint magnitude between groups, timepoints, or both
Glutamate release in nucleus accumbens core
From paperNot explicitly stated in provided text
Artifact type
Endpoint measurements summarized by group or timepoint
Comparison focus
Compare endpoint magnitude between groups, timepoints, or both
Effect of transient inhibition on reinstatement responding
From paperNot explicitly stated in provided text
Artifact type
Endpoint measurements summarized by group or timepoint
Comparison focus
Compare endpoint magnitude between groups, timepoints, or both
Lever pressing behavior (reinstatement of cocaine-seeking)
From paperRaw artifact
Per-sample or per-animal endpoint measurements collected during the experiment
Processed artifact
Structured table with cleaned measurements ready for comparison
Final reported form
Summary statistics and between-group or across-timepoint comparisons
Dopamine levels in prefrontal cortex
From paperRaw artifact
Per-sample or per-animal endpoint measurements collected during the experiment
Processed artifact
Structured table with cleaned measurements ready for comparison
Final reported form
Summary statistics and between-group or across-timepoint comparisons
Glutamate release in nucleus accumbens core
From paperRaw artifact
Per-sample or per-animal endpoint measurements collected during the experiment
Processed artifact
Structured table with cleaned measurements ready for comparison
Final reported form
Summary statistics and between-group or across-timepoint comparisons
Effect of transient inhibition on reinstatement responding
From paperRaw artifact
Per-sample or per-animal endpoint measurements collected during the experiment
Processed artifact
Structured table with cleaned measurements ready for comparison
Final reported form
Summary statistics and between-group or across-timepoint comparisons
Acquisition
Collect raw experimental outputs with enough metadata to preserve sample identity, condition, and timing.
Preprocessing / cleaning
Not explicitly stated in provided text
Scoring or quantification
Quantify the primary readouts for this experiment: Lever pressing behavior (reinstatement of cocaine-seeking); Dopamine levels in prefrontal cortex; Glutamate release in nucleus accumbens core; Effect of transient inhibition on reinstatement responding.
Statistical comparison
Statistical method not yet structured for this page.
Reporting output
Report representative outputs alongside summary comparisons for Lever pressing behavior (reinstatement of cocaine-seeking), Dopamine levels in prefrontal cortex, Glutamate release in nucleus accumbens core, Effect of transient inhibition on reinstatement responding.
Source links and direct wording from the methods section for validation and deeper review.
Citation
Krista McFarland et al. (2004). Limbic and Motor Circuitry Underlying Footshock-Induced Reinstatement of Cocaine-Seeking Behavior. Journal of Neuroscience
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