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 microM) 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 alpha(2)-adrenoceptor antagonist idazoxan (100 microM) 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 microM) 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 microM) or BRL 44408 (10 microM) into the LC were combined with prazosin (10 microM), 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.
Pudovkina
Olga L
OL
Department of Biomonitoring and Sensoring, University Center for Pharmacy, University of Groningen, Deusinglaan 1, 9712AV Groningen, The Netherlands. o_pudovkina@yahoo.com
Westerink
Ben H C
BH
D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000818:Animals; D001923:Brain Chemistry / Q000187:drug effects / Q000502:physiology*; D004347:Drug Interactions; D008125:Locus Coeruleus / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D017551:Microdialysis; D017397:Prefrontal Cortex / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D011942:Receptors, Adrenergic, alpha / Q000502:physiology*; D013997:Time Factors; D014851:Wakefulness / Q000502:physiology
D000317:Adrenergic alpha-Antagonists; D011942:Receptors, Adrenergic, alpha