Sound vibration, a non-invasive stress: antagonism by diazepam.
Rats, subjected to sound-vibration stress, showed an abrupt increase in plasma corticosterone (CS). This stimulation was reliably produced using a Burgess brand "vibro-graver," a standard tool used for engraving. With the tool set at "8" or coarse, the barrel of the tool was placed on the animal's flank and the point held against the side of the metal cage for 15 s. Plasma CS increased to 29.3 +/- 4.7 micrograms/dl at 15 min and 15.7 +/- 1.8 micrograms/dl at 30 min. These levels were significantly higher than animals pretreated with diazepam, 5 mg/kg i.v., 2 h prior to stimulation (9.2 +/- 2.0 and 7.4 +/- 1.5 micrograms/dl, respectively). Animals which were pretreated with CGS-8216 (a mixed agonist/antagonist at the benzodiazepine receptor), 2 mg/kg i.v., 30 min prior to diazepam had the protective effects of diazepam abolished. Sound/vibration produced a significant elevation in plasma CS in animals given CGS-8216 alone; but, this elevation was significantly lower than in vehicle-treated controls. This comparatively lower plasma CS level suggests a partial-agonist, diazepam-like effect by CGS-8216. Experiments were done in conscious unrestrained male Sprague-Dawley rats with chronic i.v. catheters. Except for 15 s stimulation exposure, all animals remained isolated in sound-attenuated one-way vision boxes for the duration of the serial blood sampling. Control stimulation exposure involved similar handling without turning on the engraving tool. These results demonstrate: 1) the usefulness of this tool to provide a repeatable stress stimulus; 2) the ability of diazepam to abolish the stress response; 3) that CGS-8216 can antagonize the action of diazepam; and 4) a demonstration of the partial agonist effects of CGS-8216.
Eisenberg
R M
RM
University of Minnesota, School of Medicine, Department of Pharmacology, Duluth 55812.
D000161:Acoustic Stimulation / Q000009:adverse effects*; D000818:Animals; D001569:Benzodiazepines / Q000494:pharmacology; D003345:Corticosterone / Q000097:blood; D003975:Diazepam / Q000037:antagonists & inhibitors / Q000627:therapeutic use*; D008297:Male; D011720:Pyrazoles / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013315:Stress, Psychological / Q000097:blood / Q000188:drug therapy*; D014732:Vibration / Q000009:adverse effects*
D011720:Pyrazoles; D001569:Benzodiazepines; C033830:2-phenylpyrazolo(4,3-c)quinolin-3(5H)-one; D003975:Diazepam; D003345:Corticosterone