The nucleus accumbens core (NAc) is important for integrating and providing information to downstream areas about the timing and value of anticipated reward. Although NAc is one of the first brain regions to be affected by drugs of abuse, we still do not know how neural correlates related to reward expectancy are affected by previous cocaine self-administration. To address this issue, we recorded from single neurons in the NAc of rats that had previously self-administered cocaine or sucrose (control). Neural recordings were then taken while rats performed an odor-guided decision-making task in which we independently manipulated value of expected reward by changing the delay to or size of reward across a series of trial blocks. We found that previous cocaine self-administration made rats more impulsive, biasing choice behavior toward more immediate reward. Further, compared to controls, cocaine-exposed rats showed significantly fewer neurons in the NAc that were responsive during odor cues and reward delivery, and in the reward-responsive neurons that remained, diminished directional and value encoding was observed. Lastly, we found that after cocaine exposure, reward-related firing during longer delays was reduced compared to controls. These results demonstrate that prior cocaine self-administration alters reward-expectancy encoding in NAc, which could contribute to poor decision making observed after chronic cocaine use.
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.
Addiction has long been characterized by diminished executive function, control, and impulsivity management. In particular, these deficits often manifest themselves as impairments in reversal learning, delay discounting, and response inhibition. Understanding the neurobiological substrates of these behavioral deficits is of paramount importance to our understanding of addiction. Within the cycle of addiction, periods during and after withdrawal represent a particularly difficult point of intervention in that the negative physical symptoms associated with drug removal and drug craving increase the likelihood that the patient will relapse and return to drug use in order to abate these symptoms. Moreover, it is often during this time that drug induced deficits in executive function hinder the ability of the patient to refrain from drug use. Thus, it is necessary to understand the physiological and behavioral changes associated with withdrawal and drug craving-largely manifesting as deficits in executive control-to develop more effective treatment strategies. In this review, we address the long-term impact that drugs of abuse have on the behavioral and neural correlates that give rise to executive control as measured by reversal learning, delay discounting, and stop-signal tasks, focusing particularly on our work using rats as a model system.
The insula contributes to behavioral control and is disrupted by substance abuse, yet we know little about the neural signals underlying these functions or how they are disrupted after chronic drug self-administration. Here, male and female rats self-administered either cocaine (experimental group) or sucrose (control) for twelve consecutive days. After a one-month withdrawal period, we recorded from insula while rats performed a previously learned rewardguided decision-making task. Cocaine-exposed rats were more sensitive to value manipulations and were faster to respond. These behavioral changes were accompanied by elevated counts of neurons in the insula that increased firing to reward. These neurons also fired more strongly at related to immediate reward. These changes in neural activity likely contribute to impaired 55 decision-making and impulsivity observed after drug use.
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