Behavioral and neurochemical effects of prenatal halothane

Permanent neurobehavioral toxicological effects have been theorized to occur at the lowest doses of a toxic agent if exposure occurs during early development compared to exposure during adulthood. Data are reviewed showing the exposure to 10 ppm of halothane from conception to day 60 of life post-partum led to adult rats (>/= 135 days of age) which were hyperalgesic to electric footshock and which committed 30% more errors learning a light-dark discrimination to escape footshock, or learning the shortest path to a food reward in a maze. Exposure only during adulthood to 10 ppm of halothane (from day 60 of life onwards) had no effects. To determine prenatal periods sensitive to halothane, rats were exposed to 12,500 ppm of halothane (with 35% oxygen) on day 3, 10, or 17 of gestation. As adults (>/= 75 days of age) day 3- and day 10-exposed rats, but not day 17-exposed rats, were hyperalgesic and committed 40% more errors in learning a visual discrimination to escape footshock. Food and water consumption, body weight, and running wheel activity were unaffected. Finally, adult rats exposed to 10, 50, or 100 ppm of halothane from conception to day 28 postpartum had 15% less 5-hydroxyindoleacetic acid in brain, but normal 5-hydroxytryptophan, noradrenalin, and dopamine. The possibility is discussed that the hyperalgesia noted above results from a permanently reduced turnover of brain serotonin produced by halothane present in brain at days 10-15 of gestation.