Научная статья на тему 'Cholinergic mechanisms of nucleus reticularis pontis oralis in the regulation of rapid eye movement sleep in pigeons'

Cholinergic mechanisms of nucleus reticularis pontis oralis in the regulation of rapid eye movement sleep in pigeons Текст научной статьи по специальности «Фармакология»


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Текст научной работы на тему «Cholinergic mechanisms of nucleus reticularis pontis oralis in the regulation of rapid eye movement sleep in pigeons»

9th multidisciplinary international

Conference of Biological Psychiatry

«Stress and Behavior»

Proceedings of the 9th International Multidisciplinary Conference «Stress and behavior» Saint-Petersburg, Russia, 16-19 May 2005 Editor: Allan V. Kalueff, PhD



A.A. Guselnikova

Sechenov Institute of Evolutionary Physiology and Biochemistry RAS, St. Petersburg, Russia

It is now well known that switching off a group of cells of the brainstem — Nucleus reticularis pontis oralis (NRPO) — primarily relates to loss of electrophysiological parameters of Rapid Eye Movement Sleep (REMS). NRPO participates in direct influence on cortical desynchronization of REMS supplying with endogenous brain stimulation. NRPO is a critical structure involved in the regulation of sleep and wakefulness (Jones, 1991;Vertes, 1993). More recent reports show that microinjections of a carbachol agonist acetylcholine (stimulating cholinergic systems in NRPO) increases neuronal discharges and produces elecrophysiologocal parameters of REMS in cats, rats (Bourgin et al.,1995; Garzon et al., 1997; Kinney et al., 1998) and pigeons (Guselnikova, 2002). Investigations in rats detected that muscarinic (M-)cholinoreceptors of reticular formation regulate acetylcholine release and trigger REMS (Salin-Pascual et al, 1998). It is unclear which type of cholinoreceptors (M- or N-) activation generates REMS in birds. 6 adult pigeons (Columba livia) were housed at a free movement condition with ambient temperature 24—25 °C on a 12:12 h light/dark cycle, with ad libitum food and water. Computer registration (1-s epoch for 24 h) of EEG, electrooculogram (EOG), electromyogram (EMG), ECG, brain temperature (Tbr) and foot skin temperature (Tfs) was used to assess sleep-wakefulness state and somatovisceral function. Bilateral microinjections of cholinergic agonist carbachol (0.2 mkg/0.1 mkl), arecoline (0.6 mkg/0.2 mkl), nicotine (0.3 mkg/0.2 mkl) and antagonist of cholinergic receptor amizil (0.6 mkg/0.2mkl) into mesencephalic part of NRPO were performed through cannulas implantated by coordinate atlas (Karten, Hodos, 1967) at the onset of dark phase. The control animals were injected with saline. Microinjections of carbachol stimulating M- and N-cholinoreactive systems for the first 2 h of dark phase induced a dramatic increase in REMS (increased number of episodes) and a suppressed of NonREM sbeep (Non REMS) compared to controls. During 3-h dark phase, the REMS total time (TT) and Non REMS was not different from the control. The level of wakefulness during all night declined. Microinjections of M-cholinoreceptor agonist arecoline were always accompanied by a less expressive rise of REMS TT (due to the quantity and the duration of increased episodes) for the first 2 h of dark phase (vs. those of carbachol). Microinjections of N-cholinoreceptor agonist nicotine at the same time induced lesser rise of REMS TT compared to arecoline. Microinjections of M-cholinoreceptor antagonist amizil did not alter REMS TT vs. control. The important characteristics of REMS are somatovisceral functions: EEG, EOG, EMG, ECG, Tbr and Tfs. The natural REMS is always characterized by EEG desynchronization, rapid eye movement, atonia, «tachicardia» at the end of the episodes, increased Tbr and decreased Tfs (vasoconstriction), where episodes of REMS always alternated with episodes of Non REMS. Microinjections of cholino/agonists were not always accompanied by all these parameters. Carbachol induced the flashes of rapid eye movement in EOG at the end of the episodes, and the changes of Tbr/Tfs differed from natural REMS characteristics. Besides, REMS episodes began almost immediately after carbachol injections and alternated with episodes of drowsiness, but not with SWS like in intact animals. The microinjections of arecoline always increased Tbr, although vasoconstriction was not found in all episodes. EOG frequently was not consistent with parameters of natural REMS and «tachycardia» which rarely occurred at the end of the episodes. Nicotine produced REMS with all characteristics found to be more similar to natural sleep. Our study shows that activation of M-cholinoreceptors by arecoline and N-cholinoreceptors by nicotine

Psychopharmacol. Biol. Narcol. 2005. Vol. 5, N 2. P. 894 Psyhopharmacology & biological narcology

ISSN 1606-8181

results in an increase in TT REMS. Carbachol, which stimulates M- and N-cholinoreactive systems, induces the most robust increase in TT REMS. Carbachol and arecoline alter some somatovisceral REMS characteristics. Effects of nicotine are more similar to natural REMS. The study was supported by the Program of DBS RAS «Integrative mechanisms of wakefulness-sleep cycle regulation».

Psychopharmacol. Biol. Narcol. 2005. Vol. 5, N 2. P. 894 Psyhopharmacology & biological narcology

ISSN 1606-8181