Stress in mice increases intrinsic pentobarbitone sensitivity by a predominantly pharmacodynamic mechanism.
1. Mice were swum for 3 min at room temperature. 2. After this stress 'sleeping time' in response to pentobarbitone was increased by over 70%. 3. Loss of 'righting reflex' occurred in these stressed animals at brain concentrations of pentobarbitone which were 40% lower than those needed for 'sleep' in the unstressed mice, indicating a true increase in sensitivity to the drug. 'Waking' (the return of the righting reflex) occurred at identical levels in both groups. 4. Kinetic analysis showed that the rates of absorption, elimination and transfer between plasma and brain were slower in the swum than in the unswum mice, probably because of the reduced body temperatures produced by the swimming.
Carmody
J J
JJ
School of Physiology and Pharmacology, University of New South Wales, Sydney, Australia.
Graham
G G
GG
Ruigrok
M A
MA
D000818:Animals; D001921:Brain / Q000378:metabolism; D004342:Drug Hypersensitivity / Q000209:etiology / Q000378:metabolism; D005260:Female; D051379:Mice; D008807:Mice, Inbred BALB C; D010424:Pentobarbital / Q000493:pharmacokinetics / Q000494:pharmacology*; D012890:Sleep / Q000187:drug effects; D013312:Stress, Physiological / Q000378:metabolism* / Q000503:physiopathology; D013997:Time Factors
D010424:Pentobarbital