Modulation of theta rhythmicity in the medial septal neurons and the hippocampal electroencephalogram in the awake rabbit via actions at noradrenergic alpha 2-receptors

The modulation of the firing discharge of medial septal neurons and of the hippocampal electroencephalogram (EEG) mediated by actions on alpha2-adrenoreceptors (ARs) was investigated in awake rabbits. Bilateral i.c.v. infusion of a relatively low dose (0.5 mug) of the alpha2-AR agonist clonidine produced a reduction in the theta rhythmicity of both medial septal neurons and the hippocampal EEG. In contrast, a high dose of clonidine (5 mug) increased the percentage and degree of rhythmicity of theta bursting medial septal neurons as well as the theta power of the hippocampal EEG. On the other hand, administration of alpha2-AR antagonist idazoxan produced the opposite dose-dependent effect. While a low dose of the antagonist (20 mug) produced an increase in both the theta rhythmicity of medial septal neurons and the theta power of the hippocampal EEG, a high dose (100 mug) caused a reduction of theta rhythmicity in both the medial septum and hippocampus. These results suggest that low doses of alpha2-ARs agents may act at autoreceptors regulating the synaptic release of noradrenaline, while high doses of alpha2-ARs drugs may have a predominant postsynaptic action. Similar results were observed after local injection of the alpha2-AR drugs into the medial septum suggesting that the effects induced by the i.c.v. infusion were primarily mediated at the medial septal level. We suggest that noradrenergic transmission via the postsynaptic alpha2-ARs produces fast and strong activation of the septo-hippocampal system in situations that require urgent selective attention to functionally significant information (alert, aware), whereas the action via the presynaptic alpha2-ARs allows a quick return of the activity to the initial level. (C) 2003 IBRO. Published by Elsevier Science Ltd. All rights reserved.