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 o f centrally acting drugs. Female Sabra rats were exposed to a single d ose of gamma irradiation (5.3 Gy). Four days later, when both the cell ular and the humoral immune responses were impaired, they received an i.v. infusion of either phenobarbital (0.8 mg/min), ethanol (16.3 mg/m in), pentylenetetrazol (PTZ; 0.618 mg/min), or theophylline (as aminop hylline; 2 mg/min). The infusion was stopped at the onset of the pharm acologic end point-loss of righting reflex for the depressant agents o r maximal seizures for the stimulant drugs-and the concentrations of t he neuroactive drugs at that point were determined. In the ethanol exp eriment, blood samples were also taken upon awakening. The radiation-i nduced immunosuppression significantly decreased the CNS sensitivity t o the depressant action of both phenobarbital and ethanol as indicated by the higher CSF phenobarbital concentrations required to induce sle ep 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 alt er the pharmacodynamics of the two convulsant drugs (theophylline and PTZ).