Ligands of the CB2 cannabinoid receptors augment activity of the conventional antidepressant drugs in the behavioural tests in mice

• Published in: Behavioural brain research 2020-01, Vol.378, p.112297, Article 112297
• Main Authors: Poleszak, Ewa, Wośko, Sylwia, Sławińska, Karolina, Wyska, Elżbieta, Szopa, Aleksandra, Sobczyński, Jan, Wróbel, Andrzej, Doboszewska, Urszula, Wlaź, Piotr, Wlaź, Aleksandra, Szponar, Jarosław, Skałecki, Piotr, Serefko, Anna
• Format: Article
• Language: English
• Subjects: AM630; Animals; Antidepressant activity; Antidepressive Agents - administration & dosage; Antidepressive Agents - pharmacokinetics; Antidepressive Agents - pharmacology; Behavior, Animal - drug effects; Cannabinoid Receptor Agonists - administration & dosage; Cannabinoid Receptor Modulators - administration & dosage; Cannabinoid Receptor Modulators - pharmacokinetics; Cannabinoid Receptor Modulators - pharmacology; Cannabinoids - administration & dosage; Citalopram - administration & dosage; Drug Synergism; Escitalopram; Imipramine; Imipramine - administration & dosage; Indoles - administration & dosage; JWH133; Locomotion - drug effects; Male; Mice; Reboxetine; Reboxetine - administration & dosage; Receptor, Cannabinoid, CB2 - agonists; Receptor, Cannabinoid, CB2 - drug effects
• ISSN: 0166-4328; 1872-7549
• DOI: 10.1016/j.bbr.2019.112297

•JWH133 increases activity of conventional antidepressant drugs.•AM630 potentiates activity of conventional antidepressant drugs.•Interplay between CB2 receptor ligands and antidepressants is pharmacodynamic in nature. Although a lot of information can be found on the specific dual role of the endocannabinoid system in the emotional-related responses, little is known whether stimulation or inhibition of the cannabinoid (CB) receptors may affect the activity of the frequently prescribed antidepressant drugs. Our interests have been particularly focused on the potential influence of the CB2 receptors, as the ones whose central effects are relatively poorly documented when compared to the central effects of the CB1 receptors. Therefore, we evaluated the potential interaction between the CB2 receptor ligands (i.e., JWH133 – CB2 receptor agonist and AM630 – CB2 receptor inverse agonist) and several common antidepressant drugs that influence the monoaminergic system (i.e., imipramine, escitalopram, reboxetine). In order to assess the antidepressant-like effects we used two widely recognized behavioural tests, the mouse forced swim test (FST) and the tail suspension test (TST). Brain concentrations of the tested antidepressants were evaluated by the HPLC method. Intraperitoneal co-administration of per se ineffective doses of JWH133 (0.25 mg/kg) or AM630 (0.25 mg/kg) with imipramine (15 mg/kg), escitalopram (2 mg/kg), and reboxetine (2.5 mg/kg) significantly shortened the immobility time of mice in the FST and the TST, whereas it did not disturb their spontaneous locomotor activity. Furthermore, the brain levels of antidepressants were not changed. Summarizing, the results of the present study revealed that both activation and inhibition of the CB2 receptor function have a potential to strengthen the antidepressant activity of drugs targeting the monoaminergic system. Most probably, the described interaction has a pharmacodynamic background.