Author

G D. Fields

Date of Award

1986

Degree Type

Dissertation

Degree Name

Doctor of Philosophy

Abstract

This thesis examined the effect of selected "stimulant" and "depressant" drugs in mice and humans at increased pressures (4 and 7 ata) of air.;In mice, hyperbaric air acted to reduce amphetamine sulphate induced convulsive activity, lethality, and stereotyped licking/biting; in contrast, the locomotor stimulation was enhanced as was that produced by morphine suphate (15 and 30 mg/kg). With regard to the depressants, 7 ata air prolonged the sleep time induced by pentobarbital (45 mg/kg) but had no effect at the lower dose (35 mg/kg). Conversely exposure to hyperbaric air reduced the diphenhydramine (10, 20 mg/kg) - induced depression of activity, and generally increased not decreased the activity of alcohol (1.75 and 2.75 g/kg) - treated mice. Depression of activity with alcohol was only observed at 7 ata at the high dose and was transitory. Studies with appropriate pressures of helium/oxygen confirmed that the alterations of drug effects observed were due to N(,2).;In humans the effects of diphenhydramine (50 and 100 mg) and alcohol (0.25 and 0.375) at 5 ata air on memory and neuromuscular-coordination were determined in two studies. Hyperbaric air impaired memory but not neuromuscular coordination. The drugs, however, did not impair performance, and in general did not significantly worsen performance at pressure. The results indicate that N(,2) at pressures in the "air diving range" can modify the effects of centrally acting drugs. The modifications, however, are more complex than would be predicted by the concept that N(,2), at least at these pressures, produces a generalized depression of CNS activity. In particular the results in mice suggest that N(,2) may produce both stimulation (disinhibition) and depression of neuronal function, and that the type of modification observed may be dependent on the parameter chosen for study. These latter concepts are compatible with current concepts of anesthetic action, and it is proposed that a hypothesis of N(,2)'s effects on CNS function based on current concepts of anesthesia offers a better means of explaining the modification of drugs by hyperbaric air, then one based on older concepts.

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