Functional role of alpha1-adrenoceptors in the locus coeruleus: A microdialysis study

The present study elucidates the role of alpha(1)-adrenoreceptors in the locus coeruleus (LC) using a dual-probe microdialysis in conscious rats. One probe sampled noradrenaline in the LC, whereas the second probe sampled noradrenaline in a main projection area, the prefrontal cortex (PFC). To investigate a possible tonic activation of LC neurons by alpha(1)-adrenoceptor, the alpha(1)-antagonist prazosin (10 mu M) was infused into the LC. Extracellular noradrenaline in the LC decreased to about 50% of basal levels but no change of noradrenaline release was detected in the ipsilateral PFC. Next, the interaction between alpha(1)- and alpha(2)-adrenoceptors was investigated. Local administration of the a-adrenoceptor antagonist idazoxan (100 mu M) into the LC increased the noradrenaline release in the LC to about 400%, whereas noradrenaline release in the PFC rose to 150% of basal levels. A similar effect was seen when the Specific alpha(2A)-adrenoceptor antagonist BRL 44408 (10 PM) was infused: extracellular noradrenaline in the LC and PFC increased to about 400 and 120% of the basal levels, respectively. When infusions of idazoxan (100 mu M) or BRL 44408 (10 mu M) into the LC were combined with prazosin (10 mu M), the excitatory effects of the alpha(2)-adrenoceptor antagonists on the release of noradrenaline were strongly suppressed in the LC as well as in the ipsilateral PFC. It is concluded that alpha(1)-adrenoreceptors are involved in the regulation of LC activity. Apparently, alpha(1)- and alpha(2)-adrenoceptors have opposite roles in their function as autoreceptors; on LC cells. (C) 2005 Elsevier B.V. All rights reserved.