Functional characterization of α₁ adrenergic receptor in the rat locus coeruleus in vitro

α₁-adrenoceptor (α₁AR) is involved in the physiopathology of the central nervous system (CNS) and could constitute a therapeutic target for neurological disorders such as drug addiction or Alzheimer´s disease. α₁AR mainly couples to G_q/11 protein, which activation leads to stimulation of phospholipase C (PLC) and subsequent activation of protein kinase C (PKC). However, other G proteins (G_i, G_s) have also been described to be coupled to α₁AR receptors. The locus coeruleus (LC), the main noradrenergic nucleus in the CNS, has been shown to express α₁AR, but to date functional role of α₁AR in the adult rat brain LC remains unclear. The aim of this study was to characterize, by single-unit extracellular recordings of LC neurons, the role of α₁AR in the regulation of the firing rate (FR) of LC neurons in adult rat brain in vitro. For that purpose, we first characterize the effect of the α_1/α₂AR agonist noradrenaline (NA) in the presence and absence of the α₂AR antagonist RS 79948 (0.1 µM). Then, we investigated the signalling pathway involved in the effect of NA. Perfusion with NA (100 µM) inhibited the FR of LC neurons through activation of α₂AR. However, in the presence of the α₂-adrenoceptor (α₂AR) antagonist RS 79948 (0.1 µM) perfusion with NA increased the FR of NA neurons (stimulatory effect = 114%). The stimulatory effect of NA (100 µM) was blocked by the α₁AR antagonist WB 4101 (0.5 µM). Administration of the PKC inhibitor Go 6976 (1 µM), the G protein-coupled inwardly-rectifying potassium channel (GIRK) blocker BaCl₂ (300 µM) or PKA inhibitor H-89 (10 µM) failed to change the stimulatory effect of NA. However, NA (100 µM) induced stimulation was reduced by 64% in the presence of the G_i/o protein inactivator pertussis toxin (PTX) (500 ng·ml^-1). In conclusion, α₁AR activation stimulates the FR of NA neurons in the adult rat LC through a signalling pathway that involves activation of the G_i/o protein. It remains to be studied the mechanism by which G_i/o proteins stimulates the FR of LC neurons via α₁AR activation.