DEXTROMETHORPHAN AFFECTS VENTILATION DIFFERENTLY IN MALE AND FEMALE RATS

Subcutaneous administration of aspartic acid results in a long-lasting but reversible depression of ventilation in male but not in female ra ts. Aspartic acid acts on N-methyl-D-aspartate receptors. The present study tested the hypothesis that a noncompetitive N-methyl-D-aspartate -receptor antagonist, dextromethorphan (Dex), would depress ventilatio n in female rats and stimulate it in male rats. Moreover, Dex administ ered prior to aspartic acid should prevent the aspartic acid induced d epression of ventilation in male rats. In female rats, Dex caused a 30 % depression of ventilation relative to saline at 5 and 10 mg/kg (P < 0.01) but not at the highest dose (20 mg/kg). In male rats, Dex had no effect on ventilation. At a dose of 20 mg/kg, Dex depressed oxygen co nsumption to 50% of the saline value at all time points in female rats (P < 0.001) and in male rats 45 and 60 min after administration. The time points when Dex depressed ventilation and oxygen consumption were different in female rats, suggesting that the depression of ventilati on was not the result of a depression in oxygen consumption. During a hypercapnic challenge (7% CO2), female rats treated with 5 and 10 mg/k g of Dex exhibited a smaller increase in ventilatory response relative to saline treatment. At a dose of 20 mg/kg, the hypercapnic responsiv eness of male rats was markedly stimulated (85.8 +/- 8.95 ml/min) rela tive to saline (50.6 +/- 9.14 ml/min; P < 0.001). Finally, Dex adminis tered before aspartic acid prevented the aspartic acid-induced depress ion of ventilation in male rats. Thus, in rats, Dex has gender-specifi c effects on ventilation and these effects are not associated with cha nges in oxygen consumption.