Effects And Mechanisms Of Dopamine On Ketamine-induced Neuronal Apoptosis In The Early Developmental Rat Retina

Mounting evidence shows that general anesthetics can cause widespread neuronal apoptosis in the central nervous system of developmental animals and permanent learning and memory impairment in later life. This phenomenon has aroused wide concern about the safety of general anesthesia in infants. Recent studies have shown that deprivation of neuronal rhythmic spontaneous electrical activities can induce neuronal apoptosis during early development, but whether enhancement of these neuronal electrical activities can reduce or avoid physiological neuronal apoptosis or ketamine- induced neuronal apoptosis during the early development remains unknown. In this study, we combined the patch clamp electrophysiological recording, immunohistochemistry, RT-PCR and Western Blot etc. techniques to investigate the effects of ketamine on the developmental retinal neurons and their relationships with neuronal rhythmic spontaneous electrical activities; we further in-depth explored the possible protective mechanisms of dopamine on ketamine-induced developmental retinal apoptosis. Our study demonstrated physiological apoptosis occurred in the early developmental rat retina and ketamine significantly aggravated physiological apoptosis which mainly happened in postnatal day 7 rat retina, and this aggravation of physiological apoptosis by ketamine was dose and exposure time dependent. The suppression of neuronal rhythmic spontaneous electrical activities by ketamine depended on the developmental stages of rat retina. Forskolin( adenylate cyclase activator) and dopamine all enhanced neuronal rhythmic spontaneous electrical activities, reduced physiological and ketamine-induced apoptosis in the early developmental rat retina, but they did not affect the inhibitory effects of ketamine on the retinal rhythmic spontaneous electrical activities. Further study showed that dopamine D1 and D2 receptors, adenosine A2A receptor, c AMP/PKA signaling pathway, and G protein- coupled receptor kinase2 were all involved in the protective effects of dopamine on ketamine-induced neuronal apoptosis in the early developmental retina.