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

The present study elucidates the role of α1-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 α1-adrenoceptor, the α1-antagonist prazosin (10 μM) 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 α1- and α2-adrenoceptors was investigated. Local administration of the α2-adrenoceptor antagonist idazoxan (100 μM) 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 α2A-adrenoceptor antagonist BRL 44408 (10 μM) 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 μM) or BRL 44408 (10 μM) into the LC were combined with prazosin (10 μM), the excitatory effects of the α2-adrenoceptor antagonists on the release of noradrenaline were strongly suppressed in the LC as well as in the ipsilateral PFC. It is concluded that α1-adrenoreceptors are involved in the regulation of LC activity. Apparently, α1- and α2-adrenoceptors have opposite roles in their function as autoreceptors on LC cells.