Infralimbic projections and the extinction of cocaine seeking

Drug addiction is associated with impaired inhibitory control, making abstinence difficult for many individuals who suffer from this disorder. Therefore, elucidating the basic mechanisms that underlie inhibitory control, and how prolonged drug use may impair such mechanisms, is of critical importance for better understanding and treating those with substance use disorders. To probe these mechanisms, rats were trained to press a lever to receive a cocaine infusion. Once rats learn this task, all consequences of a lever press are removed, requiring the rat to inhibit its previously learned lever-pressing behavior, as it is no longer being rewarded with a cocaine infusion. This results in a decrease, or extinction, or lever pressing. Researchers have discovered that activity in the infralimbic cortex is critically important for learning to inhibit lever pressing during extinction procedures. However, it is unknown how the infralimbic cortex fits into a larger circuitry within the brain.

The present work addressed these issues by inhibiting the activity infralimbic projections to two regions, the nucleus accumbens shell and the amygdala, both known to be involved in other aspects of motivated behaviors, including cocaine seeking. Inhibiting these pathways impaired extinction learning, suggesting that activity in both pathways is critical for learning that a lever press no longer produces a cocaine infusion. The present work also identified structural alterations within the infralimbic cortex that related to how well the rat learned to inhibit its lever pressing during extinction. Together, the present work identifies components of a larger inhibitory circuit, potentially driven by structural alterations within the infralimbic cortex.