The interaction of adenosine and dopamine in modulating the consequences of central nervous system oxygen toxicity

Hyperbaric oxygen (HBO) refers to pure oxygen with a pressure greater than 1 atmospheres absolute (ATA), and when the pressure is too high, it can cause convulsive attacks. Adenosine and dopamine have been shown to be closely associated with HBO-induced convulsion seizures, and their receptors exhibited a coexisting relationship of mutual antagonism on the membrane of nerve cells. We explored the influence of adenosine and dopamine interplay on the occurrence of oxygen convulsion. Rats were individually exposed to HBO of 6 ATA and treated with adenosine, dopamine, and their receptor modulators separately and jointly, with the latency of convulsion onset recorded. In addition, after administering adenosine to rats and exposing them to HBO for 30 min, the content of dopamine and its metabolites and the activity of enzymes related to their metabolism were measured. The results revealed that dopamine was effective in resisting convulsion (>60 min vs. 32.53 ± 5.31 min, <i>P</i> = 0.000), and low-dose adenosine partially counteracted its effect (>60 min vs. 28.18 ± 6.24 min, <i>P</i> = 0.002). The combined use of adenosine A1 and dopamine D1 receptor modulators significantly impacted the incidence of convulsion. The activation or inhibition of the A2A receptor had a particularly significant impact on convulsion, whereas modulating the D2 receptor did not affect their effects. The combination of A1 agonist and D2 agonist was highly effective in resisting convulsion (>60 min vs. 32.53 ± 5.31 min, <i>P</i> = 0.000). Exposure to HBO accelerated the metabolism of dopamine to its end products, which may be related to the enhanced activity of monoamine oxidase (MAO). Adenosine can inhibit MAO activity (0.0766 ± 0.0150 U/mg.prot vs. 0.1055 ± 0.0086 U/mg.prot, <i>P</i> = 0.004), maintaining a higher level of dopamine (1.820 ± 0.379 mg/g vs. 0.602 ± 0.087 mg/g, <i>P</i> = 0.000). The study demonstrated that dopamine plays a significant role in oxygen convulsion and adenosine can affect dopamine metabolism. The interaction between them can have a crucial impact on the occurrence of oxygen convulsion. The findings offer a novel perspective for further investigating the mechanism of oxygen convulsion and exploring effective preventive strategies.<b>NEW & NOTEWORTHY</b> The interaction between adenosine and dopamine is critically important in determining the incidence of oxygen convulsion. Simultaneous regulation of both adenosine and dopamine offers a superior approach to counteract oxygen convulsion, achieving a synergistic effect exceeding the sum of their individual impacts. These findings provide new directions and insights for future in-depth and systematic exploration of the pathogenesis of central nervous system oxygen toxicity.