Source Paper
Infralimbic Prefrontal Cortex Is Responsible for Inhibiting Cocaine Seeking in Extinguished Rats
J. Peters, R. T. LaLumiere, P. W. Kalivas
Journal of Neuroscience • 2008
Cocaine Self-Administration and Extinction Training
Objective: To determine the neural circuitry responsible for inhibiting cocaine seeking during extinction training, specifically examining the role of the infralimbic cortex and nucleus accumbens shell in suppressing drug-seeking behavior
Protocol Steps
Cocaine Self-Administration Training
Rats were trained to self-administer cocaine in operant chambers
Note: Initial phase of the experiment establishing baseline cocaine-seeking behavior
View evidence from paper
“The rat prelimbic prefrontal cortex and nucleus accumbens core are critical for initiating cocaine seeking”
Extinction Training
Rats underwent extinction training to suppress cocaine-seeking behavior following self-administration
Note: Extinction learning recruits infralimbic cortex and accumbens shell neural networks
View evidence from paper
“The infralimbic cortex and accumbens shell appear to be recruited by extinction learning because inactivation of these structures before extinction training did not alter cocaine seeking”
GABA Agonist Inhibition of Brain Nuclei
Selected brain nuclei were inhibited using GABA agonists to suppress cocaine seeking in extinguished rats
Note: GABA agonists used to inhibit infralimbic cortex, nucleus accumbens shell, prelimbic cortex, and basolateral amygdala
View evidence from paper
“The present findings using inhibition of selected brain nuclei with GABA agonists show that the suppression of cocaine seeking produced by previous extinction training required activity in the rat infralimbic cortex”
Glutamate Agonist Enhancement of Infralimbic Cortex Activity
Neuronal activity in infralimbic cortex was increased using glutamate agonist AMPA to suppress cocaine reinstatement
Note: AMPA used to increase infralimbic cortex activity in extinguished animals receiving cocaine injection
View evidence from paper
“Conversely, the reinstatement of drug seeking by a cocaine injection in extinguished animals was suppressed by increasing neuronal activity in infralimbic cortex with the glutamate agonist AMPA”
Bilateral Nucleus Accumbens Shell Inhibition
Bilateral inhibition of the nucleus accumbens shell was performed to assess effects on cocaine seeking and locomotor activity
Note: Bilateral inhibition induced cocaine seeking and increased locomotor activity
View evidence from paper
“Inhibition of the accumbens shell induced cocaine seeking in extinguished rats. However, bilateral inhibition of the shell also elicited increased locomotor activity”
Unilateral Nucleus Accumbens Shell Inhibition
Unilateral inhibition of the nucleus accumbens shell was performed to assess cocaine seeking without confounding motor activity changes
Note: Unilateral inhibition did not increase motor activity, allowing assessment of cocaine seeking independent of locomotor effects
View evidence from paper
“Unilateral inhibition of the accumbens shell did not increase motor activity, and simultaneous unilateral inactivation of the infralimbic cortex and shell induced cocaine seeking”
Combined Unilateral Inactivation of Infralimbic Cortex and Accumbens Shell
Simultaneous unilateral inactivation of both the infralimbic cortex and nucleus accumbens shell was performed
Note: Results suggest interaction between these two structures is necessary for extinction training to inhibit cocaine seeking
View evidence from paper
“Simultaneous unilateral inactivation of the infralimbic cortex and shell induced cocaine seeking, suggesting that an interaction between these two structures is necessary for extinction training to inhibit cocaine seeking”