Effect of chronic DDT exposure on pentobarbital tolerance and intolerance in the rat

Barbiturate tolerance and intolerance were studied in female albino rats. Three consecutive daily ip doses of pentobarbital (30 mg/kg) were shown to produce a significant tolerance in naive rats, with sleeping times significantly shortened on both day 2 (to 65% of control) and day 3 (to 53%). This tolerance was correlated with a significant increase in the in vitro rate of hepatic microsomal pentobarbital metabolism (235% at day 3). On day 23 (after 20 days of barbiturate abstinence) the animals exhibited an intolerance (sleeping time 126%) not associated with any change in hepatic enzyme activity. All parameters returned to control values by day 43. These results suggest that the intolerance is nonhepatogenic and likely related to enhanced CNS sensitivity. In parallel studies, chronic dietary exposure to DDT (p,p-DDT 13.1 ppm; o,p-DDT 5.3 ppm) caused increased liver enzyme activity which did not prevent the appearance of tolerance by day 3 (sleeping time 72%; barbiturate metabolism 139%) but did prevent the appearance of day 23 intolerance. The hepatic induction produced by DDT appears to offset any CNS sensitivity associated with delayed barbiturate intolerance.