Abstract:

Objective: The role of the endogenous adenosinergic system in the peripheral effect of an antidepressant drug, amitriptyline, has been demonstrated in pain models and also in cardiovascular toxicity induced by amitriptyline. We performed this study as there is no information on whether adenosine or adenosine A2A receptor antagonists have any effect on the antidepressant-like activity of amitriptyline in mice. Methods: Balb-c mice were used in experiments and forced swimming test was used to evaluate the antidepressant-like activity. Mice were injected with saline (control), amitriptyline, SCH 58261 (A2A receptor antagonist), SCH 58261 + amitriptyline, adenosine, adenosine + amitriptyline, intraperitoneally. Results: Amitriptyline decreased immobility time compared to control group at both doses. SCH 58261 did not produce antidepressant like effect in the applied dose alone. Pretreatment of amitriptyline with SCH 58261 produced stronger inhibition of immobility time than amitriptyline induced alone in the same dose. Coadministration of adenosine with amitriptyine, however, it was not decreased the anti-immobility effect of amitriptyline. However, it was not statistically significant. Conclusion: It has been demonstrated that adenosinergic system may have a role in the antidepressant-like activity of amitriptyline in mice, and pretreatment with the A2A receptor antagonist may induce a more pronounced antidepressant-like activity. We are of the opinion that this finding may be of particular importance in the case of drug resistant patients. 

Keywords: