Prior cocaine self-administration impairs attention signals in anterior cingulate cortex

Abstract

Although maladaptive decision-making is a defining feature of drug abuse and addiction, we have yet to ascertain how cocaine self-administration disrupts neural signals in anterior cingulate cortex (ACC), a brain region thought to contribute to attentional control. To address this issue, rats were trained on a reward-guided decision-making task; reward value was manipulated by independently varying the size of or the delay to reward over several trial blocks. Subsequently, rats self-administered either a cocaine (experimental group) or sucrose (control) during 12 consecutive days, after which they underwent a 1-month withdrawal period. Upon completion of this period, rats performed the previously learned reward-guided decision-making task while we recorded from single neurons in ACC. We demonstrate that prior cocaine self-administration attenuates attention and attentionrelated ACC signals in an intake-dependent manner, and that changes in attention are decoupled from ACC firing. These effects likely contribute to the impaired decision-making-typified by chronic substance abuse and relapse-observed after drug use.

Prior cocaine exposure increases firing to immediate reward while attenuating cue and context signals related to reward value in anterior insula

“…Altogether, these results replicate previous findings that rats demonstrate a preference for higher-valued rewards through their choices and reaction times, and that responding is biased towards high-valued rewards in animals previously exposed to cocaine (Brockett et al, 2018; Burton et al, 2018b, 2017; Vázquez et al, 2019). Interestingly, in contrast to previous studies, we found that cocaine-exposed rats were overall more accurate on forced-choice trials ( Fig .…”

“…In addition to reporting these novel aspects of insula encoding in control rats, we also determined how these correlates are disrupted after chronic cocaine self-administration. Our results replicate previous behavioral findings demonstrating that rats in both cocaine and control groups prefer high-valued rewards, and that this preference is exaggerated in cocaine-exposed animals (Burton et al, 2018b, 2017; Roesch et al, 2007; Roesch and Bryden, 2011; Vázquez et al, 2019). Interestingly, prior cocaine self-administration shifted the balance of encoding in insula from cues and context to reward.…”

“…Notably, we have not observed these context signals in any other brain area that we have recorded from in rats performing this task (Brockett et al, 2018; Bryden et al, 2011; Burton et al, 2018b, 2017, 2015,2014b, 2014a; Kashtelyan et al, 2012; Roesch et al, 2007, 2006, 2012; Roesch and Bryden, 2011; Takahashi et al, 2017; Vázquez et al, 2019). Thus, context-related signals related to delay and size blocks appear to be unique to insula.…”

“…Further, encoding of more immediate delivery of reward was more prominent in cocaine-exposed rats. Overall, these results suggest that heightened reward responding and lower cue and context selectivity in insula may contribute to increased impulsivity and poor decision-making observed after chronic drug use (Brockett et al, 2018; Burton et al, 2018b; Mendez et al, 2010; Roesch et al, 2007; Simon et al, 2007; Vázquez et al, 2019).…”

“…In both contexts, rats learn which option yields the preferred outcome, and maintain those expectations during delays to reward and across trial blocks while simultaneously following forced-choice rules. We have shown across several studies that rats prefer immediate over delayed reward, and large over small reward, and that rats are overall more motivated during the ‘size’ block context (Burton et al, 2018b, 2017; Roesch et al, 2007; Roesch and Bryden, 2011; Vázquez et al, 2019). Further, we have shown that rats that had previously self-administered cocaine for two weeks are more sensitive to value manipulations and exhibit faster reaction times months after drug exposure (Brockett et al, 2018; Burton et al, 2018a, 2017; Vázquez et al, 2019).…”