Prolonged Cannabidiol Treatment Lacks on Detrimental Effects on Memory, Motor Performance and Anxiety in C57BL/6J Mice

Abstract

The Cannabis plant contains more than 100 currently known phytocannabinoids. Regarding the rising consumption of the non-psychotropic phytocannabinoid cannabidiol (CBD) in people’s everyday life (e.g., beauty products, food and beverages), the importance of studies on the influence of CBD on healthy humans and rodents is evident. Therefore, the behavioral profile of CBD was investigated with a battery of behavioral tests, including motor, anxiety, and memory tests after prolonged CBD treatment. Adult C57Bl/6J wildtype (WT) mice were daily intraperitoneally injected with 20 mg/kg CBD for 6 weeks starting at two different points of ages (3 months and 5 months) to compare the influence of prolonged CBD treatment with a washout period (former group) to the effects of long term CBD treatment (current group). Our results show that CBD treatment does not influence motor performance on an accelerating Rotarod test, while it also results in a lower locomotor activity in the open field (OF). No influence of CBD on spatial learning and long term memory in the Morris Water Maze (MWM) was observed. Memory in the Novel Object Recognition test (NORT) was unaffected by CBD treatment. Two different anxiety tests revealed that CBD does not affect anxiety behavior in the Dark-Light Box (DLB) and OF test. Although, anxiety is altered by current CBD treatment in the Elevated Plus Maze (EPM). Moreover, CBD-treated C57Bl/6J mice showed an unaltered acoustic startle response (ASR) compared to vehicle-treated mice. However, current CBD treatment impairs prepulse inhibition (PPI), a test to analyze sensorimotor gating. Furthermore, prolonged CBD treatment did not affect the hippocampal neuron number. Our results demonstrate that prolonged CBD treatment has no negative effect on the behavior of adult C57Bl/6J mice.

Reduced Acoustic Startle Response and Prepulse Inhibition in the Tg4-42 Model of Alzheimer’s Disease

“…In line with our finding, Ueki et al (2006) [14] reported sensorimotor gating deficits in patients with mild AD using PPI. In a recent study, PPI confirmed sensorimotor gating deficits in early AD cases [13]. However, another PPI study did not report differences between AD patients and healthy controls [61].…”

“…Analyzing ASR in Tg4-42 mice may offer a valuable measurement when assessing the efficacy of therapeutic strategies in this mouse model. Assessing startle response is a sensitive, non-invasive, reproducible, reliable and easy measure that can even be studied without analyzing PPI [13].…”

“…Tg4-42 mice are kept on a C57Bl/6J genetic background. Homozygous 7month-old (±10 days) Tg4-42 and wildtype (WT) control mice (C57Bl/6J, Jackson Laboratories, Bar Harbor, ME, USA) were used in this study with an equal distribution of male and female animals (n = [11][12][13]. No sex-differences were detected in any of the experiments.…”

“…While PPI does not require learning, it is modulated by higher cognitive processes and PPI deficits reflect sensorimotor gating impairments and the inability to filter out irrelevant information [9,11,12]. Sensory gating deficits have been described in patients with mild and moderate AD and PPI has been discussed as a biomarker for early AD [13][14][15].…”

The effects of cannabidiol on cue- and stress-induced reinstatement of cocaine seeking behavior in mice are reverted by the CB1 receptor antagonist AM4113

“…Another possibility is that CBD-treated mice performed the stressinduced reinstatement test in an elevated state of anxiety. Although CBD shows prominent anxiolytic effects (Gonzalez-Cuevas et al, 2018;Luján et al, 2019Luján et al, , 2018, a recent report indicated that prolonged CBD treatments could induce anxiety-like states (Schleicher et al, 2019). Further experimental efforts will be needed to test this specific hypothesis.…”