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Chronic oral administration of delta-9-tetrahydrocannabinol (THC) enhances working memory in aged but not young rats

Sabrina Zequeira
University of Florida

Co-Authors: Emely Gazarov1, Alara A. G├╝venli1, Johleen Seedansingh1, Erin C. Berthold1, Alexandria Senetra1, Abhisheak Sharma1, Chris R. McCurdy1, Barry Setlow1, Jennifer L. Bizon1
1University of Florida

Cannabis is one of the most widely used drugs in the US, and individuals over the age of 65 are the fastest-growing demographic of users. As the number of older adults in the US is expected to reach 90 million by 2050, it is imperative to understand the potential cognitive impacts of cannabis use in this population. This is especially true given that cannabis use in young adults can impair cognition, and that many aged individuals already exhibit such deficits, particularly in forms of cognition supported by prefrontal cortex (PFC) and hippocampus. The effects of chronic oral administration of delta-9-tetrahydrocannabinol (THC; the major psychoactive component of cannabis) were evaluated on a delayed response task that assessed PFC-dependent working memory and a water maze task that assessed hippocampal-dependent spatial memory in young adult (5 months) and aged (23 months) Fischer 344xBrown Norway F1 hybrid rats of both sexes. Rats were trained on the delayed response task until reaching a stable baseline. In agreement with prior findings, aged rats were impaired compared to young adults, particularly at longer delays. Rats of both ages then consumed either plain gelatin or gelatin containing 1 mg/kg THC daily in their home cage. Drug was administered following daily behavioral testing to dissociate chronic from acute effects. Working memory was assessed after three weeks of daily consumption. No effects of THC were observed on working memory performance in young adult rats; however, aged rats consuming THC performed reliably better than aged rats consuming control gelatin. Rats were then trained on the water maze while continuing to consume gelatin following daily training. While aged rat performance on water maze was worse than young, no reliable effects of THC were observed at either age. These findings suggest that chronic THC does not impair, and may actually provide benefit to, cognition in older subjects. Mechanisms of this age-dependent cognitive enhancement are being explored. This work was supported by R01 AG072714, FL DoH grant 21A11 and funding from the McKnight Brain Research Foundation to BS and JLB.