A key characteristic of substance use disorder (SUD) is the continued use of drugs despite adverse consequences. In rodents, this behavioral phenotype is observed in a subset of animals that continue to self-administer drugs despite delivery of an aversive stimulus (e.g., footshock). However, these methods are difficult to use with adolescent rats, given their short developmental period (20-30 days). The current study used a modified conditioned place preference (CPP) model to examine methamphetamine-seeking behavior in an aversive environment. A two-compartment CPP apparatus with a white-dotted compartment and a black compartment was used. During a 10-day conditioning phase, adolescent male and female Sprague-Dawley rats received methamphetamine (0.0-1.0 mg/kg) and were placed in the white-dotted compartment. Rats were then tested for methamphetamine-seeking behavior (i.e., increased time in the methamphetamine-paired compartment) in a drug-free state, with free access to either the methamphetamine-paired compartment illuminated with bright white LEDs (600 lux), which rats find aversive, or the black compartment illuminated with red LEDs (30 lux). Following nine extinction sessions, reinstatement was assessed after a priming dose of methamphetamine, again with free access to both LED-lit compartments. Chronic methamphetamine exposure produced a dose-dependent effect on methamphetamine-seeking behavior. Specifically, rats conditioned with 1.0 mg/kg spent more time in the methamphetamine-paired compartment despite the bright LEDs, and this group also showed methamphetamine-seeking during reinstatement. Overall, this novel approach enables the study of persistent methamphetamine-seeking behavior in an aversive environment during adolescence, advancing efforts to understand the neurobiology of SUD in adolescents.

Measuring the neural activity of the retrosplenial cortex, we are able to analyze what is happening in the brain while mice are in pursuit of a target. Through analysis of this electrophysiological data, identification and classification of specific place, grid and other neural cells related to pursuit behaviors, we can connect them with the behaviors themselves. Understanding this functionality of the brain through electrophysiological brain mapping could be an essential step to developing technologies and treatments for the brain and brain-related diseases. It can lead to further understanding of these brain regions, and could be used to extrapolate to other behaviors, cognitions, and beyond to other animals, including humans. This study will use Neuropixel 2.0 brain probes implanted in mice to derive neural data of targeted brain regions in temporal relation to the pursuit experiment being run. Analyses are ongoing, but based on preliminary data, we anticipate finding (1) increased firing related to the pursuit itself and (2) firing patterns related to spatial cognition where relative position of the target is constantly being assessed, and predictions of where the target will move creates a reputable map and positional understanding based on patterns of cells. Results from this study would further confirm the function of the retrosplenial cortex in constant spatial cognition and its role in tracking and pursuing. Specifically, connecting the electrophysiological data itself back to observed behaviors gives a picture of what behaviors are resulted from specific neural patterns, thus tying together behaviors and the cognition preceding them.