The Effect of Immunosuppression by Total-Body Irradiation on the Pharmacodynamics of Centrally Active Drugs in Rats

The aim of this investigation was to assess whether immunosuppression induced by total-body irradiation (TBI) affects the pharmacodynamics of centrally acting drugs. Female Sabra rats were exposed to a single dose of gamma irradiation (5.3 Gy). Four days later, when both the cellular and the humoral immune responses were impaired, they received an i.v. infusion of either phenobarbital (0.8 mg/min), ethanol (16.3 mg/min), pentylenetetrazol (PTZ; 0.618 mg/min), or theophylline (as aminophylline; 2 mg/min). The infusion was stopped at the onset of the pharmacologic end point—loss of righting reflex for the depressant agents or maximal seizures for the stimulant drugs—and the concentrations of the neuroactive drugs at that point were determined. In the ethanol experiment, blood samples were also taken upon awakening. The radiation-induced immunosuppression significantly decreased the CNS sensitivity to the depressant action of both phenobarbital and ethanol as indicated by the higher CSF phenobarbital concentrations required to induce sleep in the irradiated rats versus controls (156±4 vs 133 ±5 mg/L, respectively; P < 0.05), and the higher serum ethanol concentrations at the onset and offset of sleep in the immunosuppressed group versus control values (4.6±0.2 and 1.68±0.01 vs 3.79±0.17 and 1.32±0.9 mg/mL, respectively; P < 0.04). Exposure to TBI did not alter the pharmacodynamics of the two convulsant drugs (theophylline andPTZ).