Opposite effects of α1- and β-adrenoceptor stimulation on both glutamate- and γ-aminobutyric acid-mediated spontaneous transmission in cultured rat hippocampal neurons
✍ Scribed by Ariane Croce; Hélène Astier; Max Récasens; Michel Vignes
- Publisher
- John Wiley and Sons
- Year
- 2002
- Tongue
- English
- Weight
- 422 KB
- Volume
- 71
- Category
- Article
- ISSN
- 0360-4012
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✦ Synopsis
Abstract
The effects of adrenergic receptor stimulation on spontaneous synaptic transmission were investigated in cultured rat hippocampal neurons by recording spontaneous excitatory and inhibitory postsynaptic currents (sEPSC and sIPSC). Noradrenaline (NA) inhibited sEPSC in a concentration‐dependent manner, with maximal effect at 10 μM. The α~1~‐ and α~2~‐adrenoceptor‐selective agonists cirazoline and clonidine induced an inhibition of sEPSC appearance, whereas the β‐adrenoceptor agonist isoproterenol elicited an increase. The inhibitory effect of NA was reversed by α~1~‐adrenoceptor blockade. The participation of γ‐aminobutyric acid (GABA)~B~‐receptor stimulation in the inhibitory effect of NA was further examined. GABA~B~‐receptor stimulation with baclofen induced a strong inhibition of bursting activity, which was fully reversed by the GABA~B~ antagonist CGP 55845. By itself, CGP 55845 exerted a stimulatory effect on sEPSC frequency. In the presence of CGP 55845, the inhibitory effects of cirazoline and clonidine were maintained. NA (1, 10, and 100 μM) and α‐adrenoceptor agonists decreased miniature EPSC and IPSC occurrence, whereas β‐adrenergic stimulation increased it. In 50% of the cells examined, NA (1, 10 μM) had a stimulatory effect on sIPSC, whereas, in the remaining 50% of cells, NA (1, 10 μM) had an inhibitory effect. In all the cells, 100 μM NA induced an inhibition of sIPSC. The inhibitory effect of NA was due to α~1~‐receptor stimulation, whereas the excitatory effect was due to β‐receptor stimulation. In cultured hippocampal neurons, spontaneous excitatory and inhibitory synaptic transmissions are both similarly altered by adrenoceptor stimulation. However, in a subset of cells, low concentrations of NA mediate an increase of sIPSC via β‐adrenoceptor activation. © 2002 Wiley‐Liss, Inc.