Ammonia in dipnoans plays a crucial role on neuronal homeostasis, especially for those brain areas that maintain torpor and awakening states in equilibrium. In the present study, specific a subunits of the major neuroreceptor inhibitory complex (GABA A R), which predominated during some phases of aestivation of the lungfish Protopterus annectens, turned out to be key adaptive factors of this species. From the isolation, for the first time, of the encoding sequence for GABA A R a 1 , a 4 , and a 5 subunits in Protopterus annectens, qPCR and in situ hybridization levels of a 4 transcript in thalamic (P < 0.001) and mesencephalic (P < 0.01) areas proved to be significantly higher during long aestivating maintenance states. Very evident a 5 mRNA levels were detected in diencephalon during short inductive aestivating states, whereas an a 4 /a 1 turnover characterized the arousal state. Contextually, the recovery of physiological activities appeared to be tightly related to an evident up-regulation of a 1 transcripts in telencephalic and cerebellar sites. Surprisingly, TUNEL and amino cupric silver methods corroborated apoptotic and neurodegenerative cellular events, respectively, above all in telencephalon and cerebellum of lungfish exposed to long maintenance aestivating conditions. Overall, these results tend to underlie a novel GABAergic-related ON/ OFF molecular switch operating during aestivation of the lungfish, which might have a bearing on sleeping disorders.