Involvement of NMDA receptors in the antidepressant-like action of adenosine

Background and method: in this work,the contribution of nmda receptors to the antidepressant-like effect of adenosine in the forced swimming test (fst) was investigated. results: the pretreatment of mice with nmda or d-serine was able to prevent the anti-immobility effect of either adenosine or mk-801 in the fst. in addition,the administration of a sub-effective dose of adenosine produced a synergistic effect with subeffective doses of mk-801,ketamine and zinc chloride. moreover,the immobility time of the mice treated with active doses of adenosine or n6-cyclohexyladenosine (cha) plus mk-801 was not significantly different from that obtained with adenosine,cha and mk-801 alone; by contrast,the combination between active doses of adenosine and cha plus an active dose of the tricyclic antidepressant imipramine produced a greater effect in the fst than the administration of either drug alone. conclusion: together,the results suggest that the effect of adenosine in the fst is likely dependent on the inhibition of nmda receptors mediated by the activation of adenosine a1 receptors. copyright © 2012 by institute of pharmacology polish academy of sciences.