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Anesth Analg 2007;105:89-96
© 2007 International Anesthesia Research Society
doi: 10.1213/01.ane.0000263030.13249.36

ANESTHETIC PHARMACOLOGY

The Role of Protein Kinase A in Acute Ethanol-Induced Neurobehavioral Actions in Rats

Chih-Chia Lai, PhD*{dagger}, Ting-In Kuo, MS{dagger}, and Hsun-Husn Lin, PhD{ddagger}

From the Departments of *Pharmacology and {ddagger}Physiology, {dagger}Institute of Pharmacology and Toxicology, Tzu Chi University, Hualien, Taiwan.

Address correspondence and reprint requests to Hsun-Husn Lin, PhD, Department of Physiology, Tzu Chi University, 701, Section 3, Chung-Yang Road, Hualien, Taiwan 970. Address e-mail to hlin{at}mail.tcu.edu.tw.

BACKGROUND: cAMP-dependent protein kinase (PKA) signaling pathways are involved in the regulation of ethanol-induced sedative effects in knockout mouse models. In the present study, we examined the role of PKA on the behavioral action caused by ethanol in Sprague Dawley rats.

METHODS: A loss of righting reflex (LORR) test was used to study the acute sedative effects of intraperitoneally injected ethanol. Rotarod performance was used to study the motor impairment caused by ethanol. Convulsions induced by intracerebroventricular (ICV) N-methyl-d-aspartate (NMDA) were used to evaluate ethanol’s effect on NMDA receptors. Western blot analysis was used to assay protein levels for NR1 and phosphoserine 897 on NR1 subnuits.

RESULTS: ICV pretreatment with H-9 (a nonspecific PK inhibitor) or KT 5720 (a specific PKA inhibitor) dose-dependently attenuated ethanol-induced sleeping time as assessed by LORR. ICV KT 5720 did not reduce ketamine or pentobarbital-induced sleeping time. Pretreatment with forskolin (an activator of adenylyl cyclase) or chelerythrine (a selective PKC inhibitor) had no effect on ethanol-induced LORR. Ethanol-induced motor impairment was also attenuated after pretreatment with KT 5720. Ethanol significantly inhibited NMDA-induced convulsions; the inhibitory effects of ethanol were reduced by prior ICV KT 5720, which had no significant effects on the levels of phosphoserine 897 on NMDA NR1 subunits in the several brain areas we examined.

CONCLUSIONS: Our results suggest that the PKA pathway may participate in ethanol-induced neurobehavioral changes and that NMDA receptors may be involved in the PKA regulation of ethanol’s actions.






Lippincott, Williams & Wilkins Anesthesia & Analgesia® is published for the International Anesthesia Research Society® by Lippincott Williams & Wilkins with the assistance of Stanford University Libraries' HighWire Press®. Copyright 2006 by the International Anesthesia Research Society. Online ISSN: 1526-7598   Print ISSN: 0003-2999 HighWire Press
Copyright © 2007 by the International Anesthesia Research Society.