Slow death in the leopard frog Rana pipiens: neurotransmitters and anoxia tolerance.

While frogs such as Rana temporaria are known to withstand 4-5 h anoxia at room temperature, little is known about the neurological adaptations that permit this. Previous research has shown that changes in neuroactive compounds such as glutamate and dopamine in anoxia-sensitive (mammalian) brains follow a strikingly different pattern than is observed in truly anoxia-tolerant vertebrates such as the freshwater turtle. The present study measured changes in the levels of whole brain and extracellular amino acids, and extracellular dopamine, in the normoxic and 3-4 h anoxic frog Rana pipiens, in order to determine whether their neurotransmitter responses resemble the anoxia-vulnerable or anoxia-tolerant response. Increases in whole brain serine, glycine, alanine and GABA levels were similar to those seen in anoxia-tolerant species, although the levels of glutamine, taurine and glutamate did not increase as occurs in true facultative anaerobes. Extracellular levels of aspartate, taurine and GABA also increased significantly, while glutamate levels decreased. The maintenance of low extracellular glutamate was the most significant difference between the frog and the anoxic/ischemic mammalian brain, although aspartate did increase 215% over a 4 h period of anoxia. A 12-fold increase in extracellular dopamine levels during anoxia was the biggest contrast between anoxia-tolerant vertebrates and R. pipiens. The frog could thus be an interesting model in which to examine the mechanisms of dopamine failure in early anoxia, which occurs rapidly in the mammal but over a period of hours in the 'slow death' of the anoxic frog brain.