Abstract
BackgroundThough there are several classes of antidepressant drugs available on the pharmaceutical market, depression that affects globally over 320 million people is still undertreated. Scientists have made attempts to develop novel therapeutical strategies to maximize effectiveness of therapy and minimize undesired reactions. One of the ideas is use of either dual-action agents or combined administration of two substances that affect diverse neurotransmissions. Thus, we investigated whether the selected CB receptor ligands (oleamide, AM251, JWH133, and AM630) can have an impact on the activity of bupropion and moclobemide. Bupropion belongs to the dual acting drugs, whereas moclobemide is an inhibitor of monoamine oxidase.MethodsThe mice forced swim test and the tail suspension test were applied in order to determine the potential antidepressant-like activity, whereas the HPLC method was used in order to assess the brain concentrations of the tested antidepressants.ResultsAn intraperitoneal injection of sub-effective doses of oleamide (5 mg/kg), AM251 (0.25 mg/kg), and AM630 (0.25 mg/kg) increased activity of bupropion (10 mg/kg) in both behavioural tests. Effects of moclobemide (1.5 mg/kg) were potentiated only by AM251. These results were not influenced by the hypo- or hyperlocomotion of animals.ConclusionThe outcomes of the present study revealed that particularly activation or inhibition of the CB1 receptor function may augment the antidepressant activity of bupropion, whereas only inhibition of the CB1 receptor function manages to increase activity of moclobemide. Most probably, an interplay between CB receptor ligands and bupropion or moclobemide takes place at the cellular level.
Highlights
Though there are several classes of antidepressant drugs available on the pharmaceutical market, depression that affects globally over 320 million people is still undertreated
In order to investigate the influence of CB receptor ligands on the activity of bupropion and moclobemide, we performed two worldly recognized behavioural tests that are widely used for evaluation of the antidepressant potential, i.e. the mouse forced swim test (FST) and the mouse tail suspension test (TST)
After exposure to respective combinations, i.e. oleamide–bupropion or AM251–bupropion, the tested animals were swimming for a longer period than their control counterparts and they struggled for a longer time in the TST (Fig. 1)
Summary
Though there are several classes of antidepressant drugs available on the pharmaceutical market, depression that affects globally over 320 million people is still undertreated. Over the last few decades scientists have made attempts to develop novel antidepressant drugs and/or therapeutical strategies to maximize effectiveness of therapy and minimize undesired reactions. Knowing that cannabinoid (CB) receptor ligands are able to potentiate the activity of common antidepressants, i.e. the tricyclic imipramine, selective serotonine reuptake inhibitor—escitalopram, and selective inhibitor of noradrenaline reuptake—reboxetine [6], we wanted to check whether they can affect the effects of other antidepressant drugs that have a little bit different biological targets, such as bupropion and moclobemide. In order to investigate the influence of CB receptor ligands on the activity of bupropion and moclobemide, we performed two worldly recognized behavioural tests that are widely used for evaluation of the antidepressant potential, i.e. the mouse forced swim test (FST) and the mouse tail suspension test (TST). An interplay between CB receptor ligands and bupropion or moclobemide takes place at the cellular level
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