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Rationale Previous work indicated that progesterone (PRO) reduced impulsive choice for cocaine in female but not male rats (Smethells et al. 2016). Impulsive action, typically measured by responding for a reinforcer during a signaled period of nonavailability of natural reinforcers, predicts initiation and escalation of drug use in animals and humans. The present study examined impulsive action for cocaine using progesterone (PRO) in male and female rats trained on a Go/No-go task. Objective Rats were trained on a Go/No-go task to respond for cocaine infusions (0.4 mg/kg/inf). During the “Go” component, responding was reinforced on a VI 30-s schedule; whereas, during the “No-Go” component withholding a response was reinforced on a differential reinforcement of other behavior (DRO) 30-s schedule. A response during the No-go component reset the DRO timer and served as a measure of impulsive action. After baseline responding was established, rats were pretreated with vehicle (VEH) or PRO (0.5 mg/kg), and DRO resets and responding during the Go component for cocaine were compared in males vs. females. Results DRO resets were significantly lower following PRO treatment compared to VEH in female, but not male, rats. Response rates and overall infusions during the Go component were not significantly altered by PRO in either females or males. Conclusion Treatment with PRO resulted in a sex-specific reduction in impulsive action for cocaine, while not affecting cocaine self-administration.

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Background Defensive and threat-related behaviors are common targets of investigation, because they model aspects of human mental illness. These behaviors are typically quantified by video recording and post hoc analysis. Those quantifications can be laborious and/or computationally intensive. Depending on the analysis method, the resulting measurements can be noisy or inaccurate. Other defensive behaviors, such as suppression of operant reward seeking, require extensive animal pre-training. New Method We demonstrate a method for quantifying defensive behavior (immobility or freezing) by 3-axis accelerometry integrated with an electrophysiology headstage. We tested multiple pre-processing and smoothing methods, and correlated them against two common methods for quantification: freezing as derived from standard video analysis, and suppression of operantly shaped bar pressing. We assessed these three methods' ability to track defensive behavior during a standard threat conditioning and extinction paradigm. Results The best approach to tracking defensive behavior from accelerometry was Gaussian filter smoothing of the first derivative (change score or jerk). Behavior scores from this method reproduced canonical conditioning and extinction curves at the group level. At the individual level, timepoint-to-timepoint correlations between accelerometry, video, and bar press metrics were statistically significant but modest (largest r=0.53, between accelerometry and bar press). Comparison with existing methods The integration with standard electrophysiology systems and relatively lightweight signal processing may make accelerometry particularly well suited to detect behavior in resource-constrained or real-time applications. At the same time, there were modest cross-correlations between all three methods for quantifying defensive behavior. Conclusions Accelerometry analysis allows researchers already using electrophysiology to assess defensive behaviors without the need for additional behavioral measures or video. The similarities in behavioral tracking and modest correlations between each metric suggest that each measures a distinct aspect of defensive behavior. Accelerometry is a viable alternative to current defensive measurements, and its non-overlap with other metrics may allow a more sophisticated dissection of threat responses in future experiments.