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The Effects of Oral Delta-9-THC Administration on Intertemporal Decision Making in Aged Rats

Emely Gazarov
University of Florida

Co-Authors: Marina I Waisenberg1, Christos Raptis1, Max S Gotlin1, Samantha F Pattey1, Jennifer L Bizon1, Barry Setlow1
1University of Florida

Background: With the rise in use of cannabis and cannabinoids among older adults, it is important to understand their effects on the cognitive and neural profiles in this age group. Older adults tend to exhibit greater preference for large, delayed over small, immediate rewards compared to younger adults (i.e., reduced “impulsive choice”). Although this age-related shift in intertemporal decision making is frequently framed as being beneficial, it has the potential to be maladaptive in that it can delay necessary medical procedures or other expenditures that could enhance quality of life.

Objectives: The goal of this study was to use rats to determine how acute and chronic delta-9-tetrahydrocannabinol (THC, the primary psychoactive component of cannabis) affects intertemporal decision making in aging, using an oral consumption model shown previously to differentially affect cognitive performance in young and aged rats.

Methods: Fischer 344 x Brown Norway F1 hybrid rats (N=19, 9F, 10M) were trained to make choices between two levers, one delivering a small, immediate food reward, and the other delivering a large food reward delivered after delays of varying durations. Once rats reached stable performance, they were habituated to consume 3.5 g of gelatin containing a small amount of ethanol (100 µl/kg). For acute testing, each rat received 0, 0.3, and 1 mg/kg THC gelatin in a randomized order thirty minutes before behavioral testing. Following a one-week washout period, chronic effects were assessed by administering either control or 1 mg/kg THC gelatin daily for four weeks. Task performance (percentage of large reward choices) was analyzed via repeated measures ANOVA, with drug condition as a between-subjects factor and week and delay as within-subject factors.

Results: Acute THC administration had no effect on intertemporal decision making. In contrast, chronic THC caused rats to reduced their preference for the large, delayed reward across weeks, while control showed no shifts in their preference. This was supported by a significant Week × Delay × Drug interaction (F(4,52) = 2.84, p = 0.033), suggesting that chronic THC administration increases discounting of delayed rewards (increases impulsivity) in aged rats.

Conclusions: These findings highlight the potential impact of chronic THC use on decision-making and impulsivity in aged individuals, emphasizing the need for further research to better understand cognitive effects of cannabis use in older adults. Future directions include comparisons of THC effects on decision making in young subjects and assessment of CB1 receptor expression in brain regions important for decision-making.