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Pharmacol Biochem Behav. 2019 Nov 27;188:172833. doi: 10.1016/j.pbb.2019.172833. [Epub ahead of print]

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

Author information

1
Department of Applied and Social Pharmacy, Medical University of Lublin, Chodźki 1, 20-093 Lublin, Poland. Electronic address: ewa.poleszak@umlub.pl.
2
Department of Applied and Social Pharmacy, Medical University of Lublin, Chodźki 1, 20-093 Lublin, Poland.
3
Department of Pharmacokinetics and Physical Pharmacy, Jagiellonian University Medical College, Medyczna 9, 30-688 Kraków, Poland.
4
Department of Applied and Social Pharmacy, Laboratory of Preclinical Testing, Medical University of Lublin, Chodźki 1, 20-093 Lublin, Poland.
5
Second Department of Gynecology, Medical University of Lublin, Jaczewskiego 8, 20-090 Lublin, Poland.
6
Department of Animal Physiology, Faculty of Biology and Biotechnology, Maria Curie-Skłodowska University, Akademicka 19, 20-033 Lublin, Poland.
7
Department of Pathophysiology, Medical University of Lublin, Jaczewskiego 8, 20-090 Lublin, Poland.
8
Department of Applied and Social Pharmacy, Laboratory of Preclinical Testing, Medical University of Lublin, Chodźki 1, 20-093 Lublin, Poland. Electronic address: anna.serefko@umlub.pl.

Abstract

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.

KEYWORDS:

AM251; AM630; Agomelatine; JWH133; Oleamide; Tianeptine

PMID:
31785246
DOI:
10.1016/j.pbb.2019.172833

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