The effects of acute Cannabis smoke or Δ9-THC injections on the trial-unique, nonmatching-to-location and five-choice serial reaction time tasks in male Long-Evans rats

Abstract

Executive functions including working memory (WM) and attention are altered following Cannabis exposure in humans. To test for similar effects in a rodent model, we exposed adult male rats to acute Cannabis smoke before testing them on touchscreen-based tasks that assess these executive processes. The trial-unique, delayed nonmatching-to-location (TUNL) task was used to evaluate WM, task performance at different spatial pattern separations, and response latencies. The five-choice serial reaction time task (5-CSRTT) was used to measure attention, impulsivity, perseveration, and response latencies. Rats were exposed acutely to high- Δ⁹-tetrahydrocannabinol (THC), low-CBD (Mohawk) and low-THC, high-CBD (Treasure Island) strains of Cannabis smoke using a chamber inhalation system. The effects of Cannabis smoke were directly compared to systemic Δ⁹-THC injection (3.0 mg/kg; i.p.). TUNL task performance was significantly impaired following acute high-THC smoke exposure or THC injections, but not low-THC smoke exposure, with no effects on response latencies. Fewer total trials and selection trials were also performed following THC injections. Performance was poorer for smaller separation distances in all groups. Neither acute smoke exposure, nor injected THC, impacted attentional processes, impulsivity, perseverations, or response latencies in the 5-CSRTT. Pharmacokinetic analysis of rat plasma revealed significantly higher THC levels following injections than smoke exposure 30 min following treatment. Exposure to low-THC, high-CBD Cannabis smoke significantly increased CBD in plasma, relative to the other treatments. Taken together, our results suggest that WM processes as measured by the TUNL task are more sensitive to THC exposure than the attentional and impulsivity measures assessed using the 5-CSRTT.

Keywords: 5-CSRTT; Acute smoke exposure; Attention; Cannabidiol; Cannabinoid; Pharmacokinetic; THC; TUNL; Working memory.