No evidence for functional imidazoline receptors on locus coeruleus neurons

alpha(2)-Adrenoceptor agonists inhibit the firing of locus coeruleus (LC) neurons. It was recently observed that the alpha-adrenoceptor agonists clonidine, rilmenidine and cirazoline, when injected intravenously in anaesthetized rats pretreated with the irreversible alpha(2)-adrenoceptor antagonist N-ethoxycarbonyl-2-ethoxy-1,2-dihydroquinoline (EEDQ), excite the LC. The effect was attributed to activation of I-1 imidazoline receptors. The aim of the present experiments was to characterize the direct effect of alpha(2)-adrenoceptor and I-1 imidazoline receptor agonists on LC neurons. Electrical activity of LC neurons was extracellularly recorded in midpontine slices prepared from the rat brain. Concentration-response curves were obtained for the alpha(2)-agonist noradrenaline and the mixed I-1/alpha(2)-receptor agonists clonidine, rilmenidine and moxonidine in slices without treatment and in slices treated with 6-chloro-N-methyl-2,3,4,5-tetraydro-1H-3-benzazepine (SK&F86466) or EEDQ, alpha(2)-adrenoceptor antagonists with low affinity for I-1 and I-2 imidazoline receptors, respectively. All four agonists concentration-dependently reduced the firing rate of the neurons, with full inhibition at higher concentrations. SK&F86466 shifted the concentration-response curves of the agonists to the right; the calculated antagonist dissociation constants are compatible with an effect of the agonists on alpha(2)-adrenoceptors. EEDQ completely prevented the inhibition by the agonists. Neither in SK&F86466- nor in EEDQ-treated slices was an excitation by clonidine, rilmenidine and moxonidine observed. We conclude that the LC neurons do not possess functional I-1 (and also no I-2) imidazoline receptors. The effects of noradrenaline, clonidine, rilmenidine and moxonidine on the neurons can be fully explained with an interaction with inhibitory alpha(2)-adrenoceptors (probably of the alpha(2D) subtype). The excitation of the LC by imidazoline receptor agonists under in vivo conditions, hence. is not a direct effect on the neurons of the LC.