Studies on the Role of α2‐Adrenoceptors in the Control of Synaptosomal [3H]5‐Hydroxytryptamine Release: Effects of Antidepressant Drugs
- 1 January 1986
- journal article
- Published by Wiley in Journal of Neurochemistry
- Vol. 46 (1), 218-223
- https://doi.org/10.1111/j.1471-4159.1986.tb12949.x
Abstract
The sensitivity of α2-adrenoceptors on 5-hydroxytryptamine (5-HT) nerve endings obtained from rat cerebral cortex was investigated following treatment with the antidepressant drugs desipramine (10 mg/kg/day for 21–28 days) or clorgyline (1 mg/kg/day for 21–28 days). [3H]5-HT (100 nM) was used to load cortical synaptosomes (P2) after experiments with uptake inhibitors confirmed that this concentration of amine ensured exclusive uptake into 5-HT nerve terminals. The sensitivity of K+-stimulated release of [3H]5-HT to α2-adrenoceptor occupancy was assessed in a superfusion system by means of the dose-dependent inhibition of [3H]5-HT release by clonidine. This is blocked by yohimbine (1 μM), which, when administered alone, enhances release, suggesting that endogenous catecholamines released from other synaptosomes act on these α2-heteroreceptors. The effect of addition of citalopram (1 μM) to superfusates suggests that some reuptake of [3H]5-HT occurs during superfusion. Of the tritium released into superfusates during “background” and K+-stimulated release, 17 and 90%, respectively is [3H]5-HT. The attenuation of K+-stimulated release by clonidine is apparently diminished by the chronic clorgyline regimen but not by desipramine. However, clorgyline elevates catecholamine levels, and this might increase endogenous noradrenaline (NA) efflux, which by competition with clonidine could appear to alter α2-adrenoceptor sensitivity. This possibility was investigated by depleting NA with the neurotoxin N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine (DSP4). These studies showed that the apparent effect of chronic clorgyline on α2-adrenoceptor sensitivity to clonidine was due to competition with increased levels of endogenous NA. A significant decrease in sensitivity to clonidine occurred with DSP4 alone. This study with drugs from the two major classes of antidepressants suggests that antidepressant drugs do not alter α2-heteroreceptors on serotonergic neurones.Keywords
This publication has 21 references indexed in Scilit:
- Down-regulation of β-adrenergic receptors following repeated injections of desmethylimipramine: Permissive role of serotonergic axonsNeuropharmacology, 1982
- Changes in α- and β-receptor densities in rat brain as a result of treatment with monoamine oxidase inhibiting antidepressantsNeuropharmacology, 1982
- Current concepts on the mechanisms of action of antidepressant drugsPharmacology & Therapeutics, 1981
- α2-Adrenoreceptors in rat brain are decreased after long-term tricyclic antidepressant drug treatmentBrain Research, 1981
- Presynaptic ReceptorsAnnual Review of Pharmacology and Toxicology, 1981
- Functional evidence for subsensitivity of noradrenergic α2 receptors after chronic desipramine treatmentLife Sciences, 1980
- Interaction of antidepressants with clonidine on rat brain total 3-methoxy-4-hydroxyphenylglycolCanadian Journal of Physiology and Pharmacology, 1979
- THE EFFECTS OF CHRONIC REGIMENS OF CLORGYLINE AND PARGYLINE ON MONOAMINE METABOLISM IN THE RAT BRAINJournal of Neurochemistry, 1979
- Feedback Inhibition of Brain Noradrenaline Neurons by Tricyclic Antidepressants: α-Receptor MediationScience, 1978
- Involvement of α-receptors in clonidine-induced inhibition of transmitter release from central monoamine neuronesNeuropharmacology, 1973