Benzodiazepine-like effects of inosine on punished behavior of pigeons

Behavioral effects of the putative endogenous benzodiazepine receptor ligand, inosine, were studied alone and in combination with the benzodiazepine antagonist Ro 15-1788. Keypeck responses were maintained by food under a multiple fixed-interval 3-min, fixed-interval 3-min schedule of food delivery. Under the multiple schedule, the first response after 3 min produced food in the presence of either white (no punishment) or red keylights and, in addition, each 30th response produced a brief electric shock (punishment) when the keylight was red. Inosine increased the low rates of punished responding (10-100 mg/kg IM) and the higher rates of unpunished responding (30 mg/kg). The benzodiazepine antagonist Ro 15-1788 (0.03 mg/kg, IM) antagonized the rate-increasing effects of inosine but had no effect when given alone. Combinations of inosine (30 mg/kg) with higher doses of Ro 15-1788 (0.1-1 mg/kg) decreased responding much like Ro 15-1788 alone. The marked rate-decreasing effects of 1000 mg/kg inosine were not affected by concurrent administration of Ro 15-1788 (0.01-1 mg/kg). The behavioral effects of inosine alone resembled effects of benzodiazepines but not those of benzodiazepine antagonists. The response rate-increasing effects of inosine may be due to its benzodiazepine receptor binding properties, whereas the rate decreases produced by higher doses of inosine appear to be unrelated to benzodiazepine receptors.