These results suggest the utility of an SSFO-based approach for enhancing activity in a structure without driving specific patterns of neuronal firing. However, the utility of an SSFO-based approach for axon terminal stimulation remains unclear. Moreover, these results suggest that the ability of the IL to reduce cocaine seeking depends, at least in part, on rats first having undergone extinction training.

The infralimbic and prelimbic (IL and PL, respectively) regions of the medial prefrontal cortex regulate the control of drug-seeking behavior. However, their roles in cocaine seeking in a discriminative stimulus (DS)-based self-administration task are unclear. To address this issue, male Sprague-Dawley rats were trained on a DS task in which, on a trial-by-trial basis, a DS+ indicated that a lever press would produce a cocaine infusion, whereas a distinct DS− indicated that a lever press would produce nothing. IL and PL inactivation via GABA receptor activation decreased performance accuracy and disinhibited behavioral responding on DS− trials, resulting in greater lever pressing during the DS− presentation. This was accompanied by a decrease in cocaine infusions obtained, a finding confirmed in a subsequent experiment using a standard FR1 cocaine self-administration paradigm. We repeated the DS study using a food reward and found that inactivation of each region decreased performance accuracy but had no effect on the total number of food pellets earned. Additional experiments with the cocaine DS task found that dopamine receptor blockade in the IL, but not PL, reduced performance accuracy and disinhibited behavioral responding on DS− trials, whereas AMPA receptor blockade in the IL and PL had no effect on performance accuracy. These findings strongly suggest that, in a DS-based self-administration task in which rats must actively decide whether to engage in lever pressing (DS+) or withhold lever pressing (DS−) on a trial-by-trial basis, both the IL and PL contribute to the inhibitory control of drug-seeking behavior.

No abstract

Over the past decades, research has targeted the neurobiology regulating cocaine-seeking behaviors, largely in the hopes of identifying potential targets for the treatment of cocaine addiction. Although much of this work has focused on those systems driving cocaine seeking, recently, studies examining the inhibition of cocaine-related behaviors have made significant progress in uncovering the neural systems that attenuate cocaine seeking. Such systems include the infralimbic cortex, nucleus accumbens shell, and hypothalamus. Research in this field has focused largely on the infralimbic cortex, as activity in this region appears to attenuate cocaine seeking during reinstatement and contribute to extinction learning. However, an overarching theory of function for this region that includes its role in other types of reward seeking and learning remains to be determined. Furthermore, the precise relationship between other regions involved in attenuating cocaine-seeking behavior and the infralimbic cortex remains unclear. Recent advances in the use of viral vectors combined with optogenetics, chemogenetics, and other approaches have greatly affected our capacity to investigate those systems inhibiting behavior dependent on cocaine-associated memories. This review will present current understanding regarding the neurobiology underlying the inhibition of such behaviors, especially focusing on the extinction of such memories, and explore how viral-vector targeting of specific brain circuits has begun to alter, and will continue to enrich, our knowledge regarding this issue.

Infralimbic cortical (IL) manipulations indicate that this region mediates extinction learning and suppresses cocaine seeking following cocaine self‐administration. However, little work has recorded IL activity during the inhibition of cocaine seeking due to the difficulty of determining precisely when cocaine‐seeking behaviour is inhibited within a cocaine‐seeking session. The present study used in vivo electrophysiology to examine IL activity across extinction as well as during cocaine self‐administration and reinstatement. Sprague–Dawley rats underwent 6‐h access cocaine self‐administration in which the response lever was available during discrete signalled trials, a procedure which allowed for the comparison between epochs of cocaine seeking versus the inhibition thereof. Subsequently, rats underwent extinction and cocaine‐primed reinstatement using the same procedure. Results indicate that theta rhythms (4–10 Hz) dominated IL local‐field potential (LFP) activity during all experimental stages. During extinction, theta power fluctuated significantly surrounding the lever press and was lower when rats engaged in cocaine seeking versus when they withheld from doing so. These patterns of oscillatory activity differed from self‐administration and reinstatement stages. Single‐unit analyses indicate heterogeneity of IL unit responses, supporting the idea that multiple neuronal subpopulations exist within the IL and promote the expression of different and even opposing cocaine‐seeking behaviours. Together, these results are consistent with the idea that aggregate synaptic and single‐unit activity in the IL represent the engagement of the IL in action monitoring to promote adaptive behaviour in accordance with task contingencies and reveal critical insights into the relationship between IL activity and the inhibition of cocaine seeking.