Authors:

Victoria M. Petty

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While many believe that cannabis use during pregnancy poses no risk, human epidemiological and animal studies indicate that prenatal cannabinoid exposure (PCE) can lead to long-lasting changes in cognitive and emotional processes. This study aims to investigate the effects of PCE on anxiety-like behaviors using a trace-fear conditioning paradigm, a hippocampus-dependent associative learning task, followed by fear extinction, which depends on the medial prefrontal cortex (mPFC). In trace fear conditioning, rats are presented with a tone (neutral stimulus) followed by a 1-second foot shock (aversive stimulus), separated by a trace interval, a stimulus-free period that requires hippocampal and mPFC involvement for memory formation. After a 240-second inter-trial interval (ITI), the procedure is repeated multiple times. Primary dependent measures include freezing during baseline (to assess general activity levels) and freezing during the trace interval (to evaluate fear expression). On day 2, contextual fear memory retention is tested by placing the animals back into the original training chamber for five minutes with no stimuli, measuring freezing as an index of memory recall. Next, animals are placed in a novel context for extinction training, consisting of 40 trials where the tone is presented without shock. Freezing behavior during the first eight trials is analyzed to assess retention of the tone-shock association. On day 3, an extinction retention test is conducted, consisting of eight tone presentations after a one-minute baseline period to assess how well fear extinction is maintained over time. We hypothesize that PCE will impair trace-fear extinction, leading to heightened anxiety-like behavior, indicated by increased freezing responses during extinction trials. This effect may result from disrupted hippocampal-prefrontal connectivity, altering the neural circuits responsible for associative learning and fear regulation. These findings will contribute to a deeper understanding of how prenatal cannabis exposure affects long-term hippocampal function, learning, and anxiety-related behaviors.

Source:

Auburn University / Harrison College of Pharmacy / 2025

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Co-authors:

Victoria M. Petty