Prior cannabis vapor exposure impairs pattern separation in rodents of multiple ages but is rescued by citicoline administration.

Vaporized THC or cannabis extract impairs spatial pattern separation—a specific type of memory—in male and female rats tested at adolescence, young adulthood, and middle adulthood. These deficits emerged during early abstinence from THC exposure and were rescued by citicoline injections, particularly when given during memory encoding or consolidation. Vehicle-exposed rats showed no impairment, and citicoline did not affect their performance. The deficits recovered during prolonged abstinence. The findings suggest citicoline may repair THC-induced cognitive deficits, though the mechanism remains unclear.

Study at a glance

Abstract

Rates of cannabis use continue to rise, however, the neurocognitive effects are not fully characterized. Deficitsin memory processes, especially in adolescents, have been reportedfollowing exposure toΔ9-tetrahydrocannabinol (THC), the main psychoactive componentin cannabis. Treatments addressing these deficits have been unsuccessful. Here, we test the hypothesis that vaporized THC/cannabis extract will impair spatial pattern separation at several ages, as assessed by the spontaneous location recognition (SLR) task. We also test the hypothesis that citicoline, a compound with memory-modulating effects, will restore THC-induced deficits in SLR. At three age points (adolescence post-natal day [PND] 36-57, young adulthood PND 177-210, and middle adulthood PND 360-393), male and female Sprague Dawley rats were longitudinally testedon the SLR task before (SLR PRE) and after (SLR POST) vaporized THC or cannabis extract exposure. This occurred via forced exposure (14 days, adolescence) or self-administration (20 days, young and/or middle adulthood). During the SLR POST, subjectsreceived saline or citicoline injections. At all ages, rats demonstrated robust performance of the SLR PRE task. During early abstinence from THC/cannabis vapor exposure, rats had impaired SLR POST performance that was rescued by citicoline administration, particularly when given during memory encoding/consolidation.Vehicle-exposed rats had intact SLR POST performance, hich was not changed by citicoline.This study is the first to demonstrate THC-induced deficits in pattern separation. While these deficits are present during early abstinence, SLR performance recovers during prolonged abstinence. Furthermore, our results indicate thatciticoline may repair THC-induced cognitivedeficits, though the mechanism requires further exploration.