Effect of 12 atmospheres helium-oxygen on the response of mice to convulsant drugs.
The mechanism by which 12 atm abs of a helium-oxygen gas mixture (heliox) antagonizes behavioral effects of ethanol is unknown. Although the threshold for pressure-reversal of general anesthesia and expression of the high pressure neurologic syndrome (HPNS) is well above 12 atm abs in mice, the ethanol antagonism by 12 atm abs heliox could result from similar underlying excitatory effects. To investigate this possibility, the behavior of water-injected control mice and the latency to convulsions in drug-injected mice were determined in 1 atm abs air and 12 atm abs heliox. Four convulsant drugs were tested: picrotoxin (2 mg/kg), dl-allylglycine (300 mg/kg), isoniazid (300 mg/kg), and l-methionine-dl-sulfoximine (170 mg/kg). Responses were videotaped to observe behavior and to measure latency to the onset of myoclonus and clonus. Results indicated no observable excitatory effects of 12 atm abs in control mice. The latency to myoclonus was significantly reduced by pressure in allylglycine-treated mice but not in mice treated with the other convulsants. Latency to clonus was not significantly altered by pressure, relative to latency at 1 atm abs heliox, for any drug tested. In conclusion, the present findings indicate that exposure to 12 atm abs heliox is not proconvulsant and, thus, the findings do not support the hypothesis that 12 atm abs heliox antagonizes ethanol indirectly via an increase in central nervous system excitability.
Syapin
P J
PJ
Alcohol and Brain Research Laboratory, School of Pharmacy, University of Southern California, Los Angeles 90033, USA.
Jones
B L
BL
Finn
D A
DA
Davies
D L
DL
Alkana
R L
RL
D000501:Allylglycine / Q000494:pharmacology; D000818:Animals; D001274:Atmospheric Pressure; D001831:Body Temperature / Q000187:drug effects; D003292:Convulsants / Q000494:pharmacology*; D006371:Helium / Q000008:administration & dosage*; D006610:High Pressure Neurological Syndrome / Q000209:etiology; D007538:Isoniazid / Q000494:pharmacology; D008297:Male; D008717:Methionine Sulfoximine / Q000494:pharmacology; D051379:Mice; D008810:Mice, Inbred C57BL; D009043:Motor Activity / Q000187:drug effects; D009207:Myoclonus / Q000139:chemically induced / Q000517:prevention & control*; D010100:Oxygen / Q000008:administration & dosage*; D010852:Picrotoxin / Q000494:pharmacology
D000501:Allylglycine; D003292:Convulsants; D006371:Helium; D007538:Isoniazid; D008717:Methionine Sulfoximine; D010100:Oxygen; D010852:Picrotoxin; C038949:heliox