Tonic regulation of the activity of noradrenergic neurons in the locus coeruleus of the conscious rat studied by dual-probe microdialysis

Abstract

In the present study, receptor specific compounds were infused via a microdialysis probe in the vicinity of the right locus coeruleus (LC). During the infusion of these compounds, the extracellular content of noradrenaline was recorded in the ipsilateral medial prefrontal cortex (mPFC) with a second microdialysis probe. Agonists and antagonists of various subtypes receptors that have been described to be localized on LC cells, were infused near the LC. The receptors investigated were: α 2-adrenergic, muscarinic, nicotinic, GABAergic (GABA A and GABA B), glutamatergic (NMDA and non-NMDA). The compounds infused were: clonidine (100 μM), idazoxan (50 μM), bicuculline (50 μM), muscimol (50 μM), baclofen (50 μM), CGP52432 (100 μM), NMDA (300 μM), CPP (300 μM), kainate (100 μM), DNQX (500 μM), oxotremorine (100 μM), atropine (10 μM), nicotine (100 μM) and mecamylamine (100 μM). Evidence was provided that GABA A, NMDA, non-NMDA glutamate, and muscarinic cholinergic receptors in the LC played roles in controlling the activity of noradrenaline neurons. The LC noradrenergic neurons were not tonically excitated by glutamatergic or cholinergic afferent neurons, and were not tonically inhibited by α 2 autoreceptors. Tonic inhibition was evident for GABAergic neurons, acting via GABA A receptors.