Persistent effect of withdrawal from intravenous methamphetamine self-administration on brain activation and behavioral economic indices involving an effort cost.

Exposure to drugs of abuse produces maladaptive changes in cost-benefit decision-making, including the evaluation of time and risk. Studies probing the effects of drug exposure on such evaluations have primarily used experimenter-administered drug regimens. Similarly, while much is known about the neural bases of effort, there have been relatively fewer investigations of the effects of drug experience on effort-based choices. We recently reported that experimenter-administered methamphetamine (meth) resulted in steeper discounting of effort for food rewards in rats, when assessed in protracted withdrawal. Here, we studied rats that underwent withdrawal from weeks of meth intravenous self-administration that later could freely select between a high effort, preferred option (progressive ratio lever pressing for sucrose pellets) versus a low effort, less preferred option (freely-available lab chow). We found decreased effort for the preferred reward and changes in a behavioral economic index demonstrating an increased sensitivity to effort in meth-experienced rats. Critically, the decreased effort for the preferred option was only present in the context of a competing option, not when it was the only option. We also confirmed rats preferred sucrose pellets over chow when both were freely available. These long-lasting changes were accompanied by decreased c-Fos activation in ventral striatum and basolateral amygdala, regions known to be important in effort-based choices. Taken together with our previous observations, these results suggest a robust and enduring effect of meth on value-based decision-making, and point to the underlying neural mechanisms that support the evaluation of an effort cost.

Anterior cingulate cortex supports effort allocation towards a qualitatively preferred option.

The anterior cingulate cortex (ACC) is known to be involved in effortful choice, yet its role in cost-benefit evaluation of qualitatively different rewards (more/less preferred), beyond magnitude differences (larger/smaller), is poorly understood. Selecting between qualitatively different options is a decision type commonly faced by humans. Here, we assessed the role of ACC on a task that has primarily been used to probe striatal function in motivation. Rats were trained to stable performance on a progressive ratio schedule for sucrose pellets and were then given sham surgeries (control) or excitotoxic NMDA lesions of ACC. Subsequently, a choice was introduced: chow was concurrently available while animals could work for the preferred sucrose pellets. ACC lesions produced a significant decrease in lever presses for sucrose pellets compared to control, whereas chow consumption was unaffected. Lesions had no effect on sucrose pellet preference when both options were freely available. When laboratory chow was not concurrently available, ACC-lesioned rats exhibited similar lever pressing as controls. During a test under specific satiety for sucrose pellets, ACC-lesioned rats also showed intact devaluation effects. The effects of ACC lesions in our task are not mediated by decreased appetite, a change in food preference, a failure to update value or a learning deficit. Taken together, we found that ACC lesions decreased effort for a qualitatively preferred option. These results are discussed with reference to effects of striatal manipulations and our recent report of a role for basolateral amygdala in effortful choice.