Protection against hypoxia-induced passive avoidance deficits: interactions between DuP 996 and ketanserin

DuP 996 and ketanserin have previously been shown to protect against experimentally induced passive avoidance (PA) deficits. In the present experiment the potential interaction between DuP 996 and ketanserin on hypoxia-induced amnesia was evaluated. Exposure to hypoxia (6.5% oxygen) produced a reliable deficit in PA retention which was attenuated by posthypoxia treatment with DuP 996 (0.01-0.1 mg/kg SC). Similar effects were found with ketanserin at 1.0 and 3.0 mg/kg SC. Coadministration of ketanserin, at a dose that did not protect against hypoxia (0.3 mg/kg SC), and DuP 996 (at doses of 0.005, 0.1, 0.03, 0.1, 0.3 and 1.0 mg/kg SC) revealed a potentiation of both previously inactive doses of DuP 996 (e.g., 0.005, 0.3, and 1.0 mg/kg SC) and an increase in the protective effect of previously active doses of DuP 996 (0.01, 0.03, 0.1 mg/kg SC). These results suggest that combined administration of DuP 996, a neurotransmitter release enhancer, with ketanserin, a serotonin (5HT) antagonist, may provide a useful treatment for dementia.