Different alpha-adrenoreceptors in the central nervous system mediating biochemical and functional effects of clonidine and receptor blocking agents

Abstract

The influence of clonidine on alpha-adrenoreceptors in the central nervous system of rats and mice has been investigated. Both functional events due to postsynaptic receptor stimulation (flexor reflex activity, motor activity) and biochemical changes have been considered. 1. 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. 2. 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). 3. 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). 4. Clonidine (0.1 mg/kg) caused a considerable inhibition of the alpha-methyltyrosine-induced disappearance of noradrenaline in the spinal cord and brain or rats and in the brain of mice. This effect of clonidine was completely antagonized by yohimbine (10 mg/kg). It was markedly 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). 5. Clonidine (0.1 mg/kg) caused an inhibition of the accumulation of Dopa after decarboxylase inhibition in the noradrenaline-rich regions of the rat central nervous system. 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). 6. The postsynaptic functional effects and the biochemical effects of clonidine may be due to stimulation of different alpha-adrenoreceptors since the two effects were inhibited differently by various alpha-adrenoreceptor blocking agents and since the two effects were produced by different doses of clonidine. The alpha-adrenoreceptors mediating the biochemical changes might be located on the noradrenergic neurones.

Effects of Tricyclic Antidepressants on Tetrabenazine-Induced Depletion of Brain Monoamines In Rats. 1. Norepinephrine

“…Yohimbine blocks presynaptic receptors, causing hypersecretion of NE (18,19). In our study, DMI enhanced the yohimbine-induced decrease of brain NE content, thereby providing evidence that inhibition of NE reuptake under hypersecretion of NE results in a decrease in NE content, and also supports the hypothesis that enhancement of TB-induced NE depletion strongly reflects a blockage of NE reuptake.…”

The thermogenic actions of α2‐adrenoceptor agonists in reserpinized mice are mediated via a central postsynaptic α2‐adrenoceptor mechanism

“…This seems unlikely for a number'-of' reasons. First, although neurochemical studies show that clonidine is selective for a2-adrenoceptors only at doses <0.1 mg kg 1 and that higher doses stimulate al-adrenoceptors (Anden et al, 1976), the other two at2-agonists are highly selective agents. Both UK-14,304 and B-HT 933 exhibit a greater than 300…”

Chronic Reboxetine Desensitizes Terminal but not Somatodendritic α2-Adrenoceptors Controlling Noradrenaline Release in the Rat Dorsal Hippocampus

“…We examined the effect of the selective a 2 -adrenoceptor agonist clonidine (Anden et al, 1976) on extracellular NA with the intracerebral microdialysis technique in conscious rats given vehicle or reboxetine for 2, 7 and 14 days. Whenever the response to systemic clonidine differed in rats given chronic vehicle or reboxetine, the drug was infused through the probe or injected into the LC to assess the functional status of terminal and somatodendritic a 2 -adrenoceptors.…”