title: Differences in response to anaesthetics and analgesics between inbred rat strains.
abstract: Differences in response to analgesic and anaesthetic drugs can partly be attributed to variations in the genetic background of experimental animals. This study was carried out to determine differences in the response of inbred rat strains to a selection of analgesics and drugs used in anaesthetic protocols. A cross between the most contrasting strains can then be phenotyped in future studies in order to localize quantitative trait loci (QTLs) involved in analgesic/anaesthetic drug sensitivity. Eight inbred strains (n = 6 rats/strain) were selected for the study: the pigmented ACI, BN and COP strains and the albino F344, LEW, SHR, WAG and WKY strains. Each rat was injected intravenously with two analgesics (buprenorphine 0.05 mg/kg and nalbuphine 1 mg/kg) and three drugs used in anaesthetic protocols (propofol 25 mg/kg, medetomidine 50 microg/kg and ketamine 10 mg/kg), respectively, using a crossover design. Analgesic responses were assessed using an analgesiometric procedure. The sleep time of the rat and, where applicable, the interval between injection and loss of righting reflex were used to determine the anaesthetic response. Six out of eight strains responded significantly different from each other to the analgesic effect of buprenorphine with the ACI strain as hyper-responder. The tail withdrawal latency at 55 degrees C of the F344 and WKY rats using buprenorphine was not significantly different from baseline tail withdrawal latencies. In this study, all strains were non-responsive to the analgesic effects of nalbuphine. The response to all three drugs used in anaesthetic protocols differed significantly among the strains. The F344 and BN strains were relatively resistant to the sedative effects of medetomidine. Use of ketamine was abandoned in the ACI and BN strains when the first two animals of both strains died soon after induction. With all three drugs the sleep time of albino rats was significantly longer compared with that of the pigmented ones. We conclude that the results from this study can be used in future studies where QTLs for the sensitivity to anaesthetic/analgesic drugs are localized.
authors.affiliation: Central Laboratory Animal Institute, Utrecht, The Netherlands. h.avsaroglu@gdl.uu.nl
authors.forename: H
authors.initials: H
authors.lastname: Avsaroglu
authors.forename: A S
authors.initials: AS
authors.lastname: van der Sar
authors.forename: H A
authors.initials: HA
authors.lastname: van Lith
authors.forename: L F M
authors.initials: LF
authors.lastname: van Zutphen
authors.forename: L J
authors.initials: LJ
authors.lastname: Hellebrekers
mesh_terms: D000698:Analgesia / Q000662:veterinary*; D000701:Analgesics, Opioid / Q000008:administration & dosage*; D000758:Anesthesia / Q000662:veterinary*; D000777:Anesthetics; D018686:Anesthetics, Intravenous / Q000008:administration & dosage*; D000818:Animals; D002047:Buprenorphine / Q000008:administration & dosage; D007649:Ketamine / Q000008:administration & dosage; D007756:Laboratory Animal Science / Q000379:methods; D008297:Male; D020926:Medetomidine / Q000008:administration & dosage; D009266:Nalbuphine / Q000008:administration & dosage; D010147:Pain Measurement / Q000187:drug effects; D015742:Propofol / Q000008:administration & dosage; D051381:Rats; D011912:Rats, Inbred ACI; D011914:Rats, Inbred BN; D011917:Rats, Inbred Lew; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D012890:Sleep / Q000187:drug effects; D013045:Species Specificity
chemical_list: D000701:Analgesics, Opioid; D000777:Anesthetics; D018686:Anesthetics, Intravenous; D002047:Buprenorphine; D007649:Ketamine; D009266:Nalbuphine; D020926:Medetomidine; D015742:Propofol