Neurochemical lesion of the locus coeruleus of the rat does not suppress the sedative effect of clonidine.

The locus coeruleus of male rats was destroyed bilaterally by injection of 6-hydroxydopamine. Rats injected with the vehicle and normal rats served as controls. Starting 20 days after the lesion, the locomotor activity of all rats was measured for 5 min every day. For the first 6 days, the lesioned rats were significantly less active than control rats; from the 7th to the 15th day, on the other hand, the locomotor activity of the two groups of rats was the same. From the 16th day onwards, the sedative effect of small doses of clonidine (2.5-100 micrograms/kg) was measured in lesioned and control animals. In spite of an almost total loss of noradrenaline in the cerebral cortex and hippocampus and a 33% loss of noradrenaline in the brain-stem of the lesioned rats, the sedative effect of clonidine was the same as in the control rats. This result suggests that the sedation produced by clonidine is not dependent on presynaptically located alpha 2-adrenoceptors.