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• W2017280192 abstract "Imidazoline binding sites have been reported to be present in the locus coeruleus (LC). To investigate the role of these sites in the control of LC neuron activity, we studied the effect of imidazolines using in vivo and in vitro single‐unit extracellular recording techniques. In anaesthetized rats, local (27 pmoles) and systemic (1 mg kg −1 , i.v.) administrations of 2‐(2‐benzofuranyl)‐2‐imidazoline (2‐BFI), a selective I‐imidazoline receptor ligand, increased the firing rate of LC cells (maximal increase: 22 ± 5%, P <0.001 and 16 ± 7%, P <0.001 respectively). Chronic pretreatment with the irreversible monoamine oxidase inhibitor clorgyline (3 mg kg −1 , i.p., every 12 h for 14 days) abolished this effect. In rat midpontine brain slices containing the LC, bath application (1 m M ) of the imidazolines 2‐BFI, 2‐(4,5‐dihydroimidaz‐2‐yl)‐quinoline (BU224), idazoxan, efaroxan, phentolamine and (2‐2‐methoxy‐1,4‐benzodioxan‐2‐yl)‐2‐imidazoline (RX821002) reversibly stimulated LC cells. The maximal effect was ∼90% except for RX821002 and efaroxan which induced smaller maximal effects (∼58% and ∼35% respectively). Simultaneous application of idazoxan and 2BFI did not lead to additive effects. Bath application of the α 2 ‐adrenoceptor antagonists, yohimbine (1–10 μ M ) and N‐ethoxycarbonyl‐1,2‐dihydroquinoline (EEDQ) (10 μ M ), failed to modify LC activity. The irreversible blockade of α 2 ‐adrenoceptors with EEDQ (10 μ M ) did not alter the effect of idazoxan or that of efaroxan. Previous application of clorgyline (10 μ M ) did not modify the excitatory effect of 2‐BFI or efaroxan. Changes in the pH of the bathing solution (6.84–7.84) did not influence the effect caused by idazoxan. Bath application of 2‐BFI (1 m M ) reversed the inhibition induced by diazoxide (300 μ M ), an ATP‐sensitive K+ channel opener, whereas application of glibenclamide (3 μ M ), an ATP‐sensitive K+ channel blocker, partially blocked the effect of 2‐BFI. This study shows that imidazoline compounds stimulate the firing rate of LC neurons. This effect is not mediated by α 2 ‐adrenoceptors nor by I 1 or I 2 ‐imidazoline receptors but involves a different subtype of imidazoline receptor. Our results indicate that this receptor is located extracellularly and modulates ATP‐sensitive K+ channels." @default.
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• W2017280192 date "1998-12-01" @default.
• W2017280192 modified "2023-10-18" @default.
• W2017280192 title "Stimulation of locus coeruleus neurons by non-I₁ /I₂ -type imidazoline receptors: an <i>in vivo</i> and <i>in vitro</i> electrophysiological study" @default.
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• W2017280192 doi "https://doi.org/10.1038/sj.bjp.0702255" @default.
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