Date of Award


Degree Type


Degree Name

Doctor of Philosophy


Operational deep-sea diving is complicated by two conditions affecting the Central Nervous System. One of these, known as Inert Gas Narcosis (IGN), is due to the presence of nitrogen (N{dollar}\sb2{dollar}) in the breathing gas, and presents signs and symptoms of progressive CNS depression similar to anaesthesia as pressure (depth) is increased. The other, referred to as the High Pressure Neurological Syndrome (HPNS) was observed when non-narcotic helium (He) was substituted for N{dollar}\sb2{dollar} to circumvent the problem of IGN. The effects are attributed to pressure per se and include, in man, tremor, EEG changes, and motor incoordination. The precise neurological changes underlying these two phenomena are unknown.;The effects of increased hydrostatic pressure and anaesthetics are mutually antagonistic, suggesting that they may exert opposite effects on central neurotransmission. This hypothesis was tested by examining the effects of various pressures of He (pressure per se) and N{dollar}\sb2{dollar} on the synthesis and release of endogenous dopamine (DA) from rat striatal slices in vitro. DA and its metabolites were quantified by High Performance Liquid Chromatography with Electrochemical Detection.;He at 24 and 100 atmospheres absolute (ATA) significantly (p {dollar}<{dollar} 0.01 and {dollar}<{dollar}0.05) enhanced the Ca{dollar}\sp{lcub}2+{rcub}{dollar} dependent component of K{dollar}\sp+{dollar} evoked release of DA, but had no effect on evoked release at 48 ATA. N{dollar}\sb2{dollar} at 12, 24, 48 or 100 ATA did not significantly affect DA release, suggesting that the narcotic property of N{dollar}\sb2{dollar} was able to protect against the effects of pressure.;Enhancement of evoked DA release by both ouabain, a cardiac glycoside, and 100 ATA He was significantly (p {dollar}<{dollar} 0.05) blocked by 3,4-dichlorobenzamil, a selective antagonist of the membrane Na{dollar}\sp+{dollar}/Ca{dollar}\sp+{dollar} exchange mechanism suggesting that pressure may exert its effects on presynaptic DA release through inhibition of the membrane Na{dollar}\sp+{dollar}/K{dollar}\sp+{dollar} pump and attendant increases in intracellular Ca{dollar}\sp{lcub}2+{rcub}{dollar} via the Na{dollar}\sp+{dollar}/Ca{dollar}\sp{lcub}2+{rcub}{dollar} exchanger.;Confirmation of the N{dollar}\sb2{dollar} reversal of pressure-augmentation of DA release was achieved with a chemically dissimilar anaesthetic agent, sodium pentobarbital, which produced significant inhibition of evoked DA release at 1 ATA air and 100 ATA He (p {dollar}<{dollar} 0.001).



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