DIFFERENT ALPHA-ADRENORECEPTORS IN CENTRAL NERVOUS-SYSTEM MEDIATING BIOCHEMICAL AND FUNCTIONAL EFFECTS OF CLONIDINE AND RECEPTOR BLOCKING-AGENTS

The influence of clonidine was investigated on .alpha.-adrenoreceptors in the CNS of rats and mice. Both functional events due to postsynaptic receptor stimulation (flexor reflex activity, motor activity) and biochemical changes were considered. Clonidine was less potent in stimulating the hindlimb flexor reflex activity of spinal rats than in inhibiting the .alpha.-methyltyrosine-induced disappearance of noradrenaline in the spinal cord and in the whole brain of rats. The increase in flexor reflex activity due to clonidine (0.4 mg/kg) was virtually completely inhibited by phenoxybenzamine (20 mg/kg) and haloperidol (10 mg/kg), was partially inhibited by yohimbine (10 mg/kg) and piperoxan (60 mg/kg) and was not significantly inhibited by yohimbine (3 mg/kg) and tolazoline (50 mg/kg). The potentiation by clonidine of the apomorphine-induced locomotor stimulation of reserpine-treated mice was almost completely inhibited by phenoxybenzamine (20 mg/kg) but was not significantly affected by yohimbine (10 or 3 mg/kg) and only slightly inhibited by tolazoline (50 mg/kg). Clonidine (0.1 mg/kg) caused a considerable inhibition of the .alpha.-methyltyrosine-induced disappearance of noradrenaline in the spinal cord and brain of rats and in the brain of mice. This effect of clonidine was completely antagonized by yohimbine (10 mg/kg). It was antagonized by yohimbine (3 mg/kg), piperoxan (60 mg/kg) or tolazoline (50 mg/kg) but not by phenoxybenzamine (20 mg/kg) or haloperidol (10 mg/kg). Clonidine (0.1 mg/kg) caused an inhibition of the accumulation of dopa after decarboxylase inhibition in the noradrenaline-rich regions of the rat CNS. This effect was counteracted by yohimbine (10 mg/kg), piperoxan (60 mg/kg) or tolazoline (50 mg/kg) but not by phenoxybenzamine (20 mg/kg). The postsynaptic functional effects and the biochemical effects of clonidine may be due to stimulation of different .alpha.-adrenoreceptors since the 2 effects were inhibited differently by various .alpha.-adrenoreceptor blocking agents and since the 2 effects were produced by different doses of clonidine. The .alpha.-adrenoreceptors mediating the biochemical changes might be located on the noradrenergic neurones.