Influence of the CB1 and CB2 cannabinoid receptor ligands on the activity of atypical antidepressant drugs in the behavioural tests in mice

• Published in: Pharmacology, biochemistry and behavior biochemistry and behavior, 2020-01, Vol.188, p.172833, Article 172833
• Main Authors: Poleszak, Ewa, Wośko, Sylwia, Sławińska, Karolina, Wyska, Elżbieta, Szopa, Aleksandra, Świąder, Katarzyna, Wróbel, Andrzej, Doboszewska, Urszula, Wlaź, Piotr, Wlaź, Aleksandra, Serefko, Anna
• Format: Article
• Language: English
• Subjects: Agomelatine; AM251; AM630; JWH133; Oleamide; Tianeptine
• ISSN: 0091-3057; 1873-5177
• DOI: 10.1016/j.pbb.2019.172833

Available data support the notion that cannabinoids, whose therapeutic value is limited due to severe adverse reactions, could be beneficial as adjunctive agents in the management of mood disorders. Polytherapy, which is superior to monotherapy in the terms of effectiveness, usually requires lower doses of the individual components. Therefore, the main objective of our study was to determine whether administration of cannabinoid (CB) receptor ligands would enhance the antidepressant activity of atypical antidepressant drugs, i.e. agomelatine and tianeptine. To evaluate the antidepressant-like potential of the tested combinations, the mouse forced swim test (FST) and the tail suspension test (TST) were used. The HPLC method was applied to assess the brain levels of agomelatine and tianeptine. Both behavioural tests demonstrated that per se an ineffective intraperitoneal dose of oleamide (CB1 receptor agonist, 5 mg/kg) potentiated the anti-immobility activity of tianeptine (15 mg/kg), whereas AM251 (CB1 receptor inverse agonist/antagonist, 0.25 mg/kg) enhanced the antidepressant effects of tianeptine and agomelatine (20 mg/kg). Intraperitoneal co-administration of per se inactive doses of AM630 (CB2 receptor inverse agonist/antagonist) and agomelatine or tianeptine significantly reduced the immobility time of animals only in the FST. CB receptor ligands did not affect the brain levels of the tested atypical antidepressants. In summary, the outcomes of the present study showed that activation and inhibition of CB1 receptors as well as inhibition of CB2 receptors may increase the antidepressant activity of tianeptine, whereas only inhibition of CB1 and CB2 receptors has a potential to augment the antidepressant activity of agomelatine. •CB1 receptor ligands potentiate the activity of tianeptine.•CB1 receptor antagonist but not an agonist augments the activity of agomelatine•CB2 receptor agonist does not increase activity of agomelatine and tianeptine.•CB2 inverse agonist/antagonist enhances activity of agomelatine and tianeptine in the FST.•Interaction between CB receptor ligands and atypical antidepressants has a pharmacodynamic nature.