Purine nucleoside--mediated immobility in mice: reversal by antidepressants.

In the forced swimming-induced immobility (despair) test model, adenosine, and 2-chloroadenosine treatment prolonged the immobilization period in mice. Dipyridamole, which is known to inhibit adenosine uptake, potentiated the adenosine effect. The purinoceptor antagonists caffeine and theophylline blocked purine nucleoside-induced enhancement of immobilization. Tricyclic antidepressants such as imipramine and desipramine, the MAO inhibitor tranylcypromine, and amphetamine, a psychostimulant, reversed purine nucleoside-induced immobility. On the other hand, quipazine, fluoxetine, and amitriptyline failed to reverse purine nucleosides-induced prolongation of immobility. None of the antidepressants in the doses investigated had any effect by themselves. Reserpine also prolonged forced swimming-induced immobility in mice. The antidepressants fluoxetine and quipazine, but not methylxanthine pretreatment, reversed reserpine-induced immobility in this test model. These results indicate that adenosine and 2-chloroadenosine probably reduce norepinephrine outflow through their action on presynaptic purinoceptors on noradrenergic neurons and thereby cause prolongation of immobility in animals.