The effects of intracerebroventricular application of 8-Br-cGMP and LY-83,583, a guanylyl cyclase inhibitor, on sleep-wake activity in rats

Ana C Ribeiro; Levente Kapás

doi:10.1016/j.brainres.2005.04.067

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The effects of intracerebroventricular application of 8-Br-cGMP and LY-83,583, a guanylyl cyclase inhibitor, on sleep-wake activity in rats

Journal article

Peer reviewed

The effects of intracerebroventricular application of 8-Br-cGMP and LY-83,583, a guanylyl cyclase inhibitor, on sleep-wake activity in rats

Ana C Ribeiro and Levente Kapás

Brain research, Vol.1049(1), pp.25-33

07/05/2005

DOI: https://doi.org/10.1016/j.brainres.2005.04.067

Handle:

https://hdl.handle.net/2376/105701

PMID: 15922313

Abstract

Second Messenger Systems - drug effects

Wakefulness - drug effects

Aminoquinolines - administration & dosage

Attention

Injections, Intraventricular

Rats

Guanylate Cyclase - metabolism

Male

Nitric Oxide - physiology

Circadian Rhythm - physiology

Electroencephalography

Sleep Stages - drug effects

Rats, Sprague-Dawley

Cyclic GMP - administration & dosage

Dose-Response Relationship, Drug

Enzyme Inhibitors - administration & dosage

Guanylate Cyclase - drug effects

Animals

Cyclic GMP - analogs & derivatives

Sleep Stages - physiology

Wakefulness - physiology

Second Messenger Systems - physiology

Electromyography

Circadian Rhythm - drug effects

Cyclic GMP is the second messenger that mediates most of the neuronal effects of nitric oxide (NO). Several lines of evidence suggest that NO-ergic mechanisms play an integral role in the regulation of vigilance. In the present study, we tested the effects of the activation of cGMP-receptive mechanisms and the inhibitor of guanylyl cyclase (GC), LY-83,583, on sleep in rats. Rats were injected intracerebroventricularly (icv) with 0.16, 4, 100, and 500 microg or 2.5 mg 8-Br-cGMP, a membrane-permeable analogue of cGMP, or 1 and 100 microg LY-83,583. Administration of 4 microg-2.5 mg 8-Br-cGMP increased wakefulness and suppressed rapid-eye-movement sleep (REMS) and non-REMS (NREMS) in rats when given before dark onset but not when given before the light period. The GC inhibitor LY-83,583 strongly promoted NREMS and suppressed REMS during the light period of the day. Furthermore, LY-83,583 induced striking increases in the delta-wave activity of the electroencephalogram (EEG) during NREMS, whereas EEG activity above the 4.5 Hz wave range was suppressed in all vigilance states. Our finding that cGMP has an arousal-promoting activity is in line with the hypothesis that NO/cGMP signaling pathway is involved in the regulation of vigilance.

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Title: The effects of intracerebroventricular application of 8-Br-cGMP and LY-83,583, a guanylyl cyclase inhibitor, on sleep-wake activity in rats
Creators: Ana C Ribeiro - Department of Biological Sciences, Fordham University, 441 E. Fordham Road, Bronx, NY 10458, USA
Levente Kapás
Publication Details: Brain research, Vol.1049(1), pp.25-33
Academic Unit: Biomedical Sciences, Department of
Publisher: Netherlands
Identifiers: 99900546729001842
Language: English
Resource Type: Journal article

The effects of intracerebroventricular application of 8-Br-cGMP and LY-83,583, a guanylyl cyclase inhibitor, on sleep-wake activity in rats

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