Administration of cannabidiol and imipramine induces antidepressant-like effects in the forced swimming test and increases brain-derived neurotrophic factor levels in the rat amygdala

Abstract

Administration of cannabidiol and imipramine induces antidepressant-like effects in the forced swimming test and increases brain-derived neurotrophic factor levels in the rat amygdala.Objective: Cannabidiol is a chemical constituent from Cannabis sativa and it has multiple mechanisms of action, including antidepressant effects. The main objective of the present study was to evaluate behavioural and molecular effects induced by administration of cannabidiol and imipramine in rats. Methods: In the present study, rats were acutely or chronically treated for 14 days once a day with saline, cannabidiol (15, 30 and 60 mg/kg) or imipramine (30 mg/kg) and the animals behaviour was assessed in forced swimming and open-field tests. Afterwards, the prefrontal cortex, hippocampus and amygdala brain-derived neurotrophic factor (BDNF) levels were assessed by enzyme-linked immunosorbent sandwich assay. Results: We observed that both acute and chronic treatments with imipramine at the dose of 30 mg/kg and cannabidiol at the dose of 30 mg/kg reduced immobility time and increased swimming time; climbing time was increased only with imipramine at the dose of 30 mg/kg, without affecting locomotor activity. In addition, chronic treatment with cannabidiol at the dose of 15 mg/kg and imipramine at the dose of 30 mg/kg increased BDNF levels in the rat amygdala. Conclusion: In conclusion, our results indicate that cannabidiol has an antidepressant-like profile and could be a new pharmacological target for the treatment of major depression.

Influence of single and repeated cannabidiol administration on emotional behavior and markers of cell proliferation and neurogenesis in non-stressed mice

“…Using nonstressed mice on a Swiss background, we replicated previous published findings that showed antidepressant-like effects of acute and repeated CBD treatment in the FST in mice (Zanelati et al, 2010) and rats (Réus et al, 2011). Here in, single CBD administration at doses of 3 and 10 mg/kg but not 30 mg/kg decreased immobility time in the TST.…”

“…The common drawback of these studies, however, was that the animals received single intraperitoneal CBD injections. Only two studies of which we are aware have reported the antidepressant-like effects of chronic CBD administration (Réus et al, 2011;Campos et al, 2013). Campos et al (2013) tested the effects of repeated CBD administration (30 mg/kg for 14 days) on the behavioral consequences of chronic unpredictable stress (CUS) in C57/B6 mice, which included anhedonia and anxiety-like behavior.…”

Plastic and Neuroprotective Mechanisms Involved in the Therapeutic Effects of Cannabidiol in Psychiatric Disorders

“…Systemic CBD treatment reduced immobility time in mice, as did the prototype tricyclic antidepressant imipramine (Zanelati et al, 2010). Similar results were shown in mice submitted to the FST or the tail suspension test (TST) (El-Alfya et al, 2010; Réus et al, 2011; Schiavon et al, 2016). More recently, the antidepressant-like effect of CBD was detected in the olfactory bulbectomy (Linge et al, 2016) and learned helplessness models (Pereira et al, 2016).…”

“…However, acute or sub-chronic CBD treatment failed to change hippocampal BDNF levels (Zanelati et al, 2010; Campos et al, 2012a). Réus et al (2011) reported similar results in three brain regions (PFC, hippocampus, and amygdala) after acute treatment with doses that induced antidepressant-like effects in rats submitted to the FST. Despite these negative results, BDNF involvement in the plastic changes induced by CBD cannot be ruled out.…”

Comment on: “Anxiogenic-like effects of chronic cannabidiol administration in rats” (Elbatsh MM, Assareh N, Marsden CA, Kendall DA, Psychopharmacology 2012)

“…Given the enigmatic nature of this CBD, it would have only been appropriate to 'cast the net' far and wide to see what happens. Previous studies which have looked at the effect of chronic CBD on BDNF protein levels in mice and rats have also used a range of doses too (Réus et al 2011;Zanelati et al 2010). Secondly, in terms of the behavioural changes in the context of anxiety, it is unclear why only the total distance travelled was reported, and the amount of time spent in inner and outer zones of the activity boxes was not mentioned (Long et al 2009).…”