The role of adenosinergic, GABAergic and benzodiazepine systems in hyperemotionality and ulcer formation in stressed rats

The effects of benzodiazepines, GABA and adenosine on distress-induced hyperemotionality and gastric lesion formation were investigated in rats. Hyperemotionality such as struggling, vocalization and defecation evoked immediately after immobilization stress were attenuated by diazepam, adenosine or adenosine plus diazepam. Conversely, pretreatment with these drugs produced rapid and potent exacerbation of gastric lesions observed after 12 h of stress. The potent adenosine A1-receptor agonist N6-cyclohexyl adenosine (CHA) markedly inhibited the distress-evoked hyperemotional behaviors and potentiated the ulceration. γ-Aminobutyric acid (GABA), muscimol, a GABA receptor agonist, and aminooxyacetic acid (AOAA), a GABA deaminase inhibitor, attenuated both stress-induced hyperemotionality and ulceration. The inhibitory effects of diazepam 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 Ro15-1788 or by picrotoxin, a chloride channel inhibitor. These results suggest that the mechanism involved in gastric lesion formation induced by immobilization stress may be different from that in hyperemotional behavior, and that the activation of GABAergic neurons may act as a central modulating factor in the hyperemotionality and ulceration induced by immobilization stress.