Previous work investigating the neurobiology of reward-seeking behaviors have indicated a connection between the dorsal agranular insular cortex (Ald) and cocaine-seeking behaviors, as blocking neuronal activity in the AId reduces cued reinstatement.  However, there is very limited research about how specific receptors within the Ald contribute to this regulation of drug seeking. Thus the current study investigated how D1 receptors in the Ald influence cocaine-seeking behaviors during reinstatement testing in rats. We hypothesized that blocking the D1 receptors would result in reduced cocaine seeking during reinstatement.

To test for this, we used male Sprague-Dawley rats that underwent two different surgeries: (i) implantation of bilateral guide cannulae aimed at the AId and (ii) implantation of an intravenous jugular catheter. After surgery, they went through cocaine self-administration for at least 12 days (2 hours daily), followed by extinction training. During extinction, rats are placed in their chambers without cocaine and our goal is that they eventually learn that pressing a lever will not give them a reward therefore resulting in a decreased activity.  Lastly, they go into the reinstatement phase, which consists of cue-induced, and cocaine-prime reinstatement. Rats received either the D1 receptor antagonist SCH 23390 or its vehicle control immediately prior to reinstatement testing. Blocking D1 receptors within the AId reduced cued and cocaine-prime reinstatement. Although previous studies have found that intra-prefrontal cortex D2 receptor blockade has no effect on cocaine seeking, we are currently examining the effects of intra-IL D2 receptor blockade during reinstatement to cocaine seeking to determine whether activity at these receptors is involved in the cocaine-seeking behaviors.

The current findings suggest that dopamine within the AId is contributing to the previous effects observed during general AId inactivation. Surprisingly, although inactivating the AId does not alter cocaine-prime reinstatement, blocking activity at D1 receptors reduces this type of reinstatement. These findings are particularly interesting given that D1 receptor blockade within other regions of the prefrontal cortex has produced similar effects, in which dopamine manipulation alters cocaine seeking despite findings showing general inactivation of the same structure has no effect.