Biomaterial Database

Comparison of the effects of acute and subchronic administration of Aroclor 1254, a commercial mixture of polychlorinated biphenyls, on pentobarbital-induced sleep time and [14C]pentobarbital disposition in mice. 1983

D L Rosin, and B R Martin

We have reported previously that polychlorinated biphenyls (PCBs) alter neurochemistry and suppress spontaneous locomotor activity in mice. The present study was initiated to determine whether orally administered (Aroclor 1254) would potentiate pentobarbital-induced sleep time. Sleep time was enhanced significantly by Aroclor 1254 (500 mg/kg) given 0 to 8 h prior to pentobarbital, with the peak effect occurring at 2 h. This effect was demonstrated to be dose-responsive in the range of 5 to 25 mg/kg given 2 h prior to pentobarbital, but only slightly larger increments in sleep time were observed with higher doses of PCBs (50, 100, 250, and 500 mg/kg). Administration of vehicle or Aroclor 1254 (30 or 100 mg/kg) for 14 successive days reduced sleep time when pentobarbital was given 45 min after the last dose of vehicle or Aroclor 1254, with a further reduction when pentobarbital was given 24 h after the last dose. As a correlate to the sleep-time studies, levels of pentobarbital and metabolites were measured in brain, liver, and plasma of mice that had received varying doses of Aroclor 1254 2 h prior to [14C]pentobarbital. Elevated levels of pentobarbital and decreased levels of metabolites were found after acute administration of Aroclor 1254 during a period of time when Aroclor 1254-treated mice were still asleep. These effects of Aroclor 1254 on pentobarbital disposition were found to be dose-dependent. Brain levels of pentobarbital in mice after 14 d of Aroclor 1254 treatment (30 mg/kg) were less than those in vehicle-treated animals, and these levels were consistent with the reduced sleep times. Thus, a correlation between pentobarbital brain levels and sleep time in both Aroclor 1254-treated and nontreated animals suggests that Aroclor 1254 does not alter pentobarbital narcosis by a direct action on the brain. Rather, acutely administered Aroclor 1254 may be augmenting sleep time by competing with pentobarbital for metabolic sites in the liver, while chronically administered Aroclor 1254 induces pentobarbital metabolism.

UI	MeSH Term	Description	Entries
D008297	Male		Males
D008815	Mice, Inbred Strains	Genetically identical individuals developed from brother and sister matings which have been carried out for twenty or more generations, or by parent x offspring matings carried out with certain restrictions. All animals within an inbred strain trace back to a common ancestor in the twentieth generation.	Inbred Mouse Strains,Inbred Strain of Mice,Inbred Strain of Mouse,Inbred Strains of Mice,Mouse, Inbred Strain,Inbred Mouse Strain,Mouse Inbred Strain,Mouse Inbred Strains,Mouse Strain, Inbred,Mouse Strains, Inbred,Strain, Inbred Mouse,Strains, Inbred Mouse
D010424	Pentobarbital	A short-acting barbiturate that is effective as a sedative and hypnotic (but not as an anti-anxiety) agent and is usually given orally. It is prescribed more frequently for sleep induction than for sedation but, like similar agents, may lose its effectiveness by the second week of continued administration. (From AMA Drug Evaluations Annual, 1994, p236)	Mebubarbital,Mebumal,Diabutal,Etaminal,Ethaminal,Nembutal,Pentobarbital Sodium,Pentobarbital, Monosodium Salt,Pentobarbitone,Sagatal,Monosodium Salt Pentobarbital
D011078	Polychlorinated Biphenyls	Industrial products consisting of a mixture of chlorinated biphenyl congeners and isomers. These compounds are highly lipophilic and tend to accumulate in fat stores of animals. Many of these compounds are considered toxic and potential environmental pollutants.	PCBs,Polychlorinated Biphenyl,Polychlorobiphenyl Compounds,Biphenyl, Polychlorinated,Biphenyls, Polychlorinated,Compounds, Polychlorobiphenyl
D001921	Brain	The part of CENTRAL NERVOUS SYSTEM that is contained within the skull (CRANIUM). Arising from the NEURAL TUBE, the embryonic brain is comprised of three major parts including PROSENCEPHALON (the forebrain); MESENCEPHALON (the midbrain); and RHOMBENCEPHALON (the hindbrain). The developed brain consists of CEREBRUM; CEREBELLUM; and other structures in the BRAIN STEM.	Encephalon
D002250	Carbon Radioisotopes	Unstable isotopes of carbon that decay or disintegrate emitting radiation. C atoms with atomic weights 10, 11, and 14-16 are radioactive carbon isotopes.	Radioisotopes, Carbon
D004347	Drug Interactions	The action of a drug that may affect the activity, metabolism, or toxicity of another drug.	Drug Interaction,Interaction, Drug,Interactions, Drug
D000818	Animals	Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA.	Animal,Metazoa,Animalia
D001140	Aroclors	Industrial chemicals which have become widespread environmental pollutants. Each aroclor is a mixture of chlorinated biphenyls (1200 series) or chlorinated terphenyls (5400 series) or a combination of both (4400 series).	Aroclor
D012890	Sleep	A readily reversible suspension of sensorimotor interaction with the environment, usually associated with recumbency and immobility.	Sleep Habits,Sleeping Habit,Sleeping Habits,Habit, Sleep,Habit, Sleeping,Habits, Sleep,Habits, Sleeping,Sleep Habit