Assessing loss of control over substance use for sucrose, alcohol and cocaine using the novel seeking under the threat of adversity (STA) task
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Substance use disorder (SUD) is a relapsing brain disorder that is characterized by loss of control over substance use, reflected by substance use despite harmful consequences. Various addiction models have been designed to capture loss of control over substance seeking, by associating operant responding for a substance with aversive stimuli such as foot shocks. We recently developed the seeking under the threat of adversity (STA) task to assess adversity in a manner that better resembles the human scenario. In the STA task, active seeking responses, during the presentation of a cue tone, lead to a 25% chance of receiving a foot shock. The aim of this study was to assess whether rats lose control over substance seeking for sucrose, alcohol, and cocaine in the STA task. Moreover, we aimed to assess whether individual differences in alcohol intake predict loss of control over seeking. The rats were trained to respond for sucrose and alcohol in an operant task. They were first trained on a fixed ratio 1 (FR1) schedule and then on random interval (RI) schedules of reinforcement, with increasing interval lengths (5 to 120s). Then, the rats were tested for control over substance use in the STA task. The rats in the alcohol batch consumed alcohol in an Intermittent Alcohol Access (IAA) setup for 2 months prior to training. Based on the level of alcohol intake, the rats were divided into low (LD) and high (HD) alcohol drinking rats. The rats in the cocaine batch underwent two sets of 10 STA sessions interspersed with extended sessions of cocaine self-administration to induce cocaine dependence. A significant and consistent suppression of sucrose seeking was observed over 14 consecutive STA sessions compared to baseline sessions. This denotes that the rats did not develop loss of control over sucrose seeking. For alcohol, we observed differential responding in the STA task for HD and LD animals. Alcohol and cocaine show decreased levels of baseline responding compared to sucrose, but also decreased suppression of responses during the task. This is indicative of loss of control for these substances and is captured by the STA task. Therefore, this model can be a great tool to investigate the neurobiological correlates of SUD, leading to improved treatment strategies in the future.