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(The FASEB Journal. 2008;22:1126.9)
© 2008 FASEB
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(The FASEB Journal. 2008;22:1126.9.)
© 2008 FASEB

1126.9

Role of NOS-NO signaling in clonidine-ethanol evoked synergistic behavioral impairment

Tara Summer Bender and Abdel A Abdel-Rahman

Pharmacology & Toxicology, East Carolina University, Greenville, NC

ABSTRACT

Clonidine-ethanol combination induces synergistic behavioral impairment in rats as measured by rotorod performance and loss of righting reflex (LORR) duration. We tested the hypothesis that NOS-NO signaling in the locus ceruleus (LC) is implicated in this interaction. Pretreatment (i.c.) with non-selective NOS inhibitor (L-NAME) or nNOS-selective inhibitor (NPLA) enhanced the impairment of rotorod performance caused by clonidine-ethanol combination. Prolongation of behavioral impairment was caused by L-NAME enhancement of the effect of ethanol, not clonidine. LORR caused by clonidine-ethanol combination was abolished by eNOS-selective inhibition (L-NIO), but not nNOS inhibition. Western blot analyses complemented the pharmacological evidence by demonstrating that clonidine-ethanol combination inhibits phosphorylation (activation) of nNOS (p-nNOS) and increases levels of phosphorylated eNOS (p-eNOS) in the LC; the change in p-nNOS, but not p-eNOS, was paralleled by similar change in LC p-ERK1/2. Therefore, NOS-derived NO in the LC is differentially involved in underlying mechanisms for clonidine-ethanol induced behavioral impairment. A decrease in nNOS-derived NO contributes to impaired rotorod performance, while an increase in eNOS-derived NO contributes to LORR duration elicited by clonidine-ethanol combination. [Supported by NIH grants 5F31AA015472 (TSB) and 2R01AA07839 (ARA)]





This Article
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Right arrow Articles by Bender, T. S.
Right arrow Articles by Abdel-Rahman, A. A
PubMed
Right arrow Articles by Bender, T. S.
Right arrow Articles by Abdel-Rahman, A. A