Neurobehavioral effects of chronic halothane exposure during developmental and juvenile periods in the rat

Chronic exposure of rats to the surgical anesthetic agent halothane during development has been found to cause both neural and behavioral impairment. Among the halothane-induced deficits are retarded synaptogenesis and impaired spontaneous alternation. It is unclear how long after birth the susceptibility to the neurotoxic effects of halothane persists. The present study compared in rats the effects of halothane exposure on synaptic density and spontaneous alternation during early and late periods of maturation. All three experimental groups were exposed to 100 parts per million of halothane for 8 h/day, 5 days/week. One group (early exposure) was exposed from day 2 of conception until 30 days after birth. The second group (late exposure) was exposed to the same amounts from day 31 until day 90 after birth. The third group (continued exposure) received both periods. The control group was treated in the same way, but was not exposed to halothane. As found in the previous study, there were greater effects of halothane on synaptogenesis than on spontaneous alternation; impairment of spontaneous alternation behavior was found only with the early exposure. Deficits in synaptic density were found with both early and late exposure, although the early exposure had more severe effects. Halting the exposure to halothane on day 30 reinstated control-like rates of synaptogenesis, but the deficit in synaptic density from the early exposure persisted into adulthood. The potent neurotoxic effect of halothane in suppressing synaptogenesis highlights not only its potential as a hazard but also its potential as an experimental tool for manipulating the rate of synaptogenesis and examining the relationship between synaptic development and behavioral maturation.