Tolerance to hexobarbital induced by short-term treatments with diazepam and tested with an EEG-threshold test in male rats.
Male Mol: SPRD rats were treated with 5 or 20 mg/kg of diazepam for 4 days. The treatment was repeated at two different ages. Diazepam was either dissolved in Intralipid (KABI, Sweden) or dispersed in gummi arabicum. Tolerance induced by the treatment was tested with an EEG-threshold technique where hexobarbital was infused intravenously on day 1, 4, 7 and 14 of the abstinence. The threshold was the dose of hexobarbital needed to induce a burst suppression of 1 sec. or more (silent second). After the first diazepam treatment significant increase in the hexobarbital threshold doses were recorded in all but one of the diazepam treated groups. The pattern varied depending on dose, age and solvent. After the second treatment tolerance was seen only when diazepam had been dissolved in Intralipid. Short term treatment with diazepam can induce cross-tolerance to hexobarbital which probably is due to an increased excitation (physical dependence) in abstinence after treatment with diazepam.
Carlsson
S
S
Karolinska Institutet, Department of Psychiatry, St Göran Hospital, Stockholm, Sweden.
Wahlström
G
G
D000818:Animals; D003975:Diazepam / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology*; D004361:Drug Tolerance; D004569:Electroencephalography / Q000187:drug effects*; D006591:Hexobarbital / Q000494:pharmacology*; D007274:Injections, Intraperitoneal; D008055:Lipids; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D012996:Solutions; D013535:Suspensions
D008055:Lipids; D012996:Solutions; D013535:Suspensions; D006591:Hexobarbital; D003975:Diazepam