Involvement of Purinergic Systems on Stress-Induced Biphasic Actions

The study was performed in an attempt to clarify the role of adenosine and benzodiazepine systems involved in stress-induced hyperemotionality and gastric ulcer formation. When rats were exposed to immobilization stress, hyperemotional behaviors such as struggling and defecation initially appeared, whereas gastric lesions occurred later. Diazepam, adenosine plus diazepam attenuated the hyperemotionality but produced rapid and potent aggravation of gastric lesions observed after 12 h of stress. The selective adenosine A_<1->receptor agonist N^6-cyclohexyl adenosine (CHA) markedly inhibited the distress-evoked hyperemotional behaviors and potentiated the ulceration. γ-Aminobutyric acid (GABA), muscimol, a GABA receptor agonist, and aminooxyacetlc acid (AOAA), a GABA deaminase inhibitor, attenuated both stress-induced hyperemotionality and ulceration. The inhibitory effects of diazepam, clonazepam and GABA on hyperemotionality were reversed, respectively, by Ro15-1788, a benzodiazepine receptor antagonist, and bicuculline, a GABA receptor antagonist. The stimulatory effect of CHA on stress ulceration was potentiated by bicuculline but was not affected by Ro 15-1788 or by picrotoxin, a chloride channel inhibitor. These results suggest that the mechanism involved in stress-induced gastric ulceration may be different from that in the hyperemotional behavior, and that when animals are exposed to aversive stress, endogenous adenosine and benzodiazepine may be intially released in order to modulate heightened emotionality producing gastric lesions by activating adenosine A-1 receptors.