Role of GABA in hypoxia tolerance, metabolic depression and hibernation—Possible links to neurotransmitter evolution

1. The roles of the inhibitory neurotransmitter GABA and the excitatory neurotransmitter glutamate in anoxic survival and anoxic death are discussed, with particular reference to the brain. 2. It is pointed out that the metabolic relationship between GABA and glutamate causes the neural levels of GABA to increase and glutamate to decrease during anoxia. 3. It is suggested that increased levels of GABA could mediate metabolic depression, and, thus, anoxic survival in ectothennic as well as endothermic vertebrates. Furthermore, evidence for a role of GABA in hibernation is discussed. 4. A hypothesis is presented suggesting that hypoxia has been a selective pressure in conserving GABA and glutamate as major inhibitory and excitatory neurotransmitters in vertebrates as well as invertebrates.