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

Abstract

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.