The nitric oxide-cGMP system of the locus coeruleus and the hypnotic action of alpha-2 adrenergic agonists

• Published in: Brain research 1999-12, Vol.849 (1), p.169-174
• Main Authors: Vulliemoz, Yvonne, Whittington, Robert A., Virag, Laszlo
• Format: Article
• Language: English
• Subjects: Adrenergic alpha-2 Receptor Agonists; Adrenergic alpha-Agonists - administration & dosage; Adrenergic alpha-Agonists - pharmacology; Adrenergic alpha-Antagonists - pharmacology; Alpha-2 adrenergic; Animals; Atipamezole; Biological and medical sciences; Cyclic GMP - metabolism; Dexmedetomidine; Dexmedetomidine - administration & dosage; Dexmedetomidine - pharmacology; Functional Laterality; Hypnotics and Sedatives - administration & dosage; Hypnotics and Sedatives - pharmacology; Hypnotics. Sedatives; Imidazoles - administration & dosage; Imidazoles - pharmacology; Locus coeruleus; Locus Coeruleus - drug effects; Locus Coeruleus - physiology; Male; Medical sciences; Microinjections; Motor Activity - drug effects; Motor Activity - physiology; Neuropharmacology; Nitric Oxide - metabolism; Nitric oxide-cGMP system; Pharmacology. Drug treatments; Posture; Psychology. Psychoanalysis. Psychiatry; Psychopharmacology; Rat; Rats; Rats, Sprague-Dawley; Reflex - drug effects; Reflex - physiology; righting reflex; Sedation; Tyrosine 3-Monooxygenase - metabolism
• ISSN: 0006-8993; 1872-6240
• DOI: 10.1016/S0006-8993(99)02147-2

Dexmedetomidine (Dex), a potent, selective alpha-2 adrenergic agonist, injected bilaterally directly into the locus coeruleus (LC), 7 μg/LC, or ip, 100 μg/kg, produced a maximum decrease in LC cGMP (−38 and −46%, respectively). Atipamezole, a selective alpha-2 adrenergic antagonist, given into the LC, 10 μg/LC, prevented the decrease in LC cGMP induced by Dex, given i.p. or into the LC. Dex produced a loss of righting reflex in about 80% of the animals, an effect which was prevented by pretreatment with atipamezole. The nitric oxide synthase antagonist l-Name injected bilaterally into the LC, 20 μg/LC, produced by itself a maximum decrease in LC cGMP of 54.5%. Dex, 100 μg/kg, ip, given after l-Name, did not further decrease LC cGMP. l-Name, by itself, did not produce a loss of righting reflex, while 6 out of 9 rats pretreated with l-Name lost their righting reflex in response to Dex. A role of the nitric oxide-cGMP system of the LC in the modulation of the hypnotic effect of alpha-2 adrenergic agonists remains uncertain.