Impairment of ketocyclazocine antinociception in rats by perinatal lead exposure.

The development of ketocyclazocine antinociception has been measured in lead-exposed rats as an indirect determinant of kappa-opioid receptor system development. Perinatal lead administration (at 300 and 1000 ppm) in the maternal drinking water from conception to weaning, impaired the antinociceptive activity of ketocyclazocine (using the paw pressure test) in 10-day-old rats. Lead caused a dose-dependent impairment of ketocyclazocine antinociception, the paw pressure threshold for 0.4 mg/kg being reduced from 207 g to 135 g in the 1000 ppm lead dose-group. Ketocyclazocine antinociception was impaired in the high-lead dose-group at 21 days, but unaffected at 30 days. Blood lead levels in 10-day-old animals were below 35 micrograms/100 ml in the low-lead dose-group and below 50 micrograms/100 ml in the high-lead dose-group. It is suggested that lead may disrupt the development of kappa-opioid receptor systems in the central nervous system and that this disruption occurs early in development.