Effect of p-chlorophenylalanine on the acquisition of tolerance to barbital.
The effect of p-chlorophenylalanine (p-CPA) pretreatment on barbital tolerance in the rat as measured by motor impairment on the moving belt test was examined in two separate studies. The first used a 2 X 2 design with doses of p-CPA (125 mg/kg) or water, and sodium barbital (300 mg/kg) or water. The treatments continued for 28 days with tests every 7 days. The p-CPA dose used was previously shown to produce and maintain greater than 95% depletion of brain serotonin (5-HT). Tolerance developed to the test doses, and even greater tolerance to the chronic treatment doses. In both cases the p-CPA slowed the development of tolerance without altering the acute response to the challenge dose of barbital. The second study involved only a p-CPA-barbital group and a water-barbital group. In this case treatment lasted for up to 8 days, with separate subgroups being tested only once each at 2-day intervals, in order to prevent the tests from affecting the rate of tolerance development. This experiment confirmed that p-CPA slowed the development of barbital tolerance. The present findings provide additional support for the possibility that 5-HT may be involved in the development of tolerance to sedatives (e.g., alcohol, pentobarbital).
D000818:Animals; D001462:Barbital / Q000008:administration & dosage / Q000097:blood / Q000494:pharmacology*; D001463:Barbiturates / Q000494:pharmacology*; D004347:Drug Interactions; D004361:Drug Tolerance; D010134:Fenclonine / Q000494:pharmacology*; D007274:Injections, Intraperitoneal; D007700:Kinetics; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D051381:Rats; D013997:Time Factors
D001463:Barbiturates; D001462:Barbital; D010134:Fenclonine