Central cholinergic depletion induced by 192 IgG-Saporin alleviates the sedative effects of propofol in rats

We examined the effect of central cholinergic depletion on the sedative pot ency of propofol in rats. Depletion was produced by intracerebroventricular administration of an immunotoxin specific to cholinergic neurones (192 IgG -Saporin; 2 mug). As a result of this lesion, acetylcholine concentration w as reduced by about 40% in the frontoparietal cortex and in the hippocampus but was essentially normal in the striatum and cerebellum. Sedation in rat s was assessed as the decrease in locomotor activity. Sedative potency of p ropofol (30 mg kg(-1) i.p.) was reduced by about 50% in rats who received t he injection of 192 IgG-Saporin as compared to controls. These results show that a central cholinergic depletion alleviates the sedative effect of pro pofol, and indicates that basal forebrain cholinergic neurones might mediat e part of the sedative/hypnotic effects of propofol.