Effects of halothane on synaptogenesis and learning behavior in rats.

Synaptic density was quantitated in the entorhinal cortex and subiculum of rats at 5, 21, 34, and 95 postnatal days. These rats were offspring of mothers that had been subjected to four different concentrations of halothane during gestation and for 60 days after birth. The exposure conditions were control, intermittent halothane (25 +/- 5 ppm or 100 +/- 5 ppm, 8 h/day, 5 days/week) and continuous halothane (25 +/- 5 ppm, 24 h/day, 7 days/week). Synaptic density in rats exposed to halothane was significantly less than in control rats. Animals exposed intermittently to 25 +/- 5 ppm halothane had higher synaptic density than animals exposed continuously to 25 +/- 5 ppm halothane or intermittently to 100 +/- 5 ppm halothane. The latter two exposure conditions exerted similar effects. The lag in synaptic development was established at 5 days postnatal and remained the same throughout the first 95 postnatal days in both the entorhinal cortex and subiculum. Delayed synaptogenesis caused by halothane was indicated by the presence of growth cones in halothane-exposed rats to 34 days compared with 21 days in the control rats. The spontaneous alternation test indicated that the delayed synaptogenesis by halothane was sufficient to suppress behavioral development. Thus, the delay in the initial synaptic maturation caused by halothane exposure in utero may result in permanent morphologic and functional deficits of the brain.