Characterization of the Anxiolytic Activity of Nunavik Rhodiola rosea

Abstract

Rhodiola rosea is a medicinal plant used by the indigenous Inuit people of Nunavik and Nunatsiavut, Eastern Canada, as a mental and physical rejuvenating agent. This traditional use led to the present investigation of R. rosea in the context of anxiety disorders. An alcohol extract of R. rosea roots was characterized phytochemically and orally administered for three consecutive days to Sprague-Dawley rats at 8 mg/kg, 25 mg/kg, and 75 mg/kg body weight. The rats were subjected to three behavioral paradigms of anxiety, including the elevated plus maze, social interaction, and contextual conditioned emotional response tests. Rhodiola rosea showed dose-dependent anxiolytic activity in the elevated plus maze and conditioned emotional response tests, with moderate effects in the higher-anxiety SI test. The active dose varied according to the anxiety test. In order to elucidate a mechanism, the extract was further tested in an in vitro GABAA-benzodiazepine receptor-binding assay, where it demonstrated low activity. This study provides the first comparative assessment of the anxiolytic activity of Nunavik R. rosea in several behaviour models and suggests that anxiolytic effects may be primarily mediated via pathways other than the GABAA-benzodiazepine site of the GABAA receptor.

Nunavik Rhodiola rosea Attenuates Expression of Fear-Potentiated Startle

“…Mean startle potentiation was significantly lower on Day 4 for rats who had received the plant extract versus the controls (indeed, the Rhodiola effects were slightly more pronounced than those of diazepam). These findings support those presented by Cayer et al [10], the only other study targeting the anxiolytic properties of Nunavik R. rosea. Although there was a significant reduction in startle potentiation on Day 4, testing in the absence of drug administration revealed some fear reinstatement.…”

“…While benzodiazepines act as potent anxiolytics, prolonged use causes dependence [25][26][27], which highlights the need for anxiolytics that act through other mechanisms. Although the Cayer et al [10] findings do not necessarily exclude the possibility of some GABAergic modulation, it suggests the primary mode of action of R. rosea is likely not GABAergic in nature. Some alternative mechanisms have been suggested to explain the anxiolytic activity of R. rosea.…”

“…Recent research has identified isolated populations of R. rosea in Nunavik, Quebec (Northern Canada), where it is used for its medicinal properties by local indigenous Inuit populations. Cayer et al [10] found that phytochemicals present in Nunavik R. rosea include those also found in European plant populations (salidroside, tyrosol, rosarin, rosavin, and rosin), and that oral administration of Nunavik R. rosea significantly attenuated expression of conditioned fear in animal models. With this in mind, our research sought to further explore the effects of Nunavik R. rosea on the expression and extinction of fear memory using fear-potentiated startle (FPS), an animal model of anxiety-related behaviors (anxiolytic compounds decreases the FPS response in rodents; see Supporting Information for rodent information and FPS apparatus details; [11]).…”

“…GABAergic signalling also plays a role in the mediation of fear expression within the central nucleus and activity-dependent plasticity in the lateral nucleus [20][21][22][23][24]. However, although many anxiolytics (e.g., diazepam) bind to GABA A receptors, Nunavik R. rosea extract and its constituent phytochemicals have low binding affinity for the GABA A benzodiazepine receptor [10]. While benzodiazepines act as potent anxiolytics, prolonged use causes dependence [25][26][27], which highlights the need for anxiolytics that act through other mechanisms.…”

“…However, Panossian et al [29] utilized a 7-day treatment protocol, which might account for the difference in glucocorticoid effects. Research suggests the primary mechanism of Nunavik R. rosea is neither glucocorticoid-based nor GABAergic (see Cayer et al [10]). Although the results of the present investigation are positive, they are limited in that they do not address this mechanism directly.…”