Continuous intraperitoneal infusion of pentobarbital: a model of barbiturate dependence in the rat.
The i.p. administration of pentobarbital using an escalating drug-dose schedule for an 11-day period resulted in the establishment of dependence on pentobarbital in male rats. Mean plasma pentobarbital levels were approximately 5 micrograms/ml during the first 3 days of the infusion period. Subsequently, there was observed a dose-responsive increase in plasma pentobarbital levels for the next 5 days, with a decline in pentobarbital levels noted during the final 3 days of the pentobarbital infusion period. Removal of pentobarbital from the infusate resulted in a rapid decline in plasma levels to less than 50% by 8 hr into the drug-free period and to barely detectable levels by 24 hr. This was correlated with a steadily increasing occurrence of withdrawal signs, with a peak occurrence by 7 to 9 hr after initiation of the drug-free period. Spontaneous locomotor activity was significantly greater in pentobarbital-dosed animals during withdrawal than in saline-infused control rats. The i.p. infusion of pentobarbital is a quick and reliable method for the study of barbiturate dependence in the rat.
D000818:Animals; D001463:Barbiturates / Q000009:adverse effects; D004195:Disease Models, Animal; D006801:Humans; D007274:Injections, Intraperitoneal; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D010424:Pentobarbital / Q000008:administration & dosage*; D051381:Rats; D011919:Rats, Inbred Strains; D013375:Substance Withdrawal Syndrome / Q000503:physiopathology; D019966:Substance-Related Disorders; D013997:Time Factors
D001463:Barbiturates; D010424:Pentobarbital