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peptide combined administration and sleep-waking cycle

In Rabbits

 

Fesenko G.N., Kovalzon V.M.

Severtsov Institute of Ecology and Evolution, Russian Academy of Science, Moscow

E-mail: g.fesenko@sevin.ru

 

комплексное введение пептидов и цикл сон-бодрствование У КРОЛИКОВ

 

Фесенко Г.Н., Ковальзон В.М.

Институт проблем экологии и эволюции им А.Н.Северцова РАН, Москва

 

 

It was hypothesized recently that combined administration of neuropeptides should be much more natural and effective than their single administration, because of peptide continuum of the entire body which is the base for general functional control (Koroleva, Ashmarin. J.Theor.Biol. Vol. 216, No. 3, 257-271, 2002). Theoretical search using mathematical vector analysis revealed several peptide combinations possible to exert a pronounced psychotropic (anxiolytic) effect, including the same of the delta sleep-inducing peptide (DSIP) with such peptides as neuropeptide-tyrosin (NPY), atrial natriuretic peptide (ANP) and calcitonin gene-related peptide (CGRP) (Koroleva, Ashmarin, 2002). As antiphobic effects usually associate to stress-protective and sleep-promoting ones, we decided to verify the above-mentioned hypothesis using our rabbit sleep test-system. We studied paired and triple combinations: DSIP+NPY, DSIP+ANP, DSIP+CGRP, DSIP+NPY+ANF, DSIP+NPY+CGRP, administrated directly to the lateral ventricle of rabbits preliminary implanted (under local procain anesthesia) with intracranial electrodes for the EEG and EMG as well as a single intracerebroventricular cannula. Otherwise the same animals treated with a saline were used as controls. Peptides (7-25 nmol per rabbit) dissolved in a saline were injected through the cannula at a volume of 60-80 μl just before the 12-hr dark period in experimental chambers. Paperless digital polygraphic recording in free-moving animals started immediately since administration and lasted for 24 hr. Preliminary data indicate only minor changes in sleep-waking cycle after a single administration of DSIP and ANP; however, single administration of NPY and CGRP produced significant increase in slow-wave sleep percentage during the first half of a dark period. No significant changes in paradoxical sleep were found. Combination of DSIP with NPY or ANP increased sleep-promoting properties of the former combination only. Also, an important augmentation in slow-wave sleep percentage and suppression of paradoxical sleep could be seen after administration of a triple combinations DSIP+NPY+CGRP and DSIP+NPY+ANР. As it is known that both DSIP and NPY can suppress stress hormonal axis, the results probably reflect secondary participation of the administrated peptides in sleep-waking control which follow their involvement into endocrine processes. Supported by RFFI (No. 02-04-48318a) and RHSF (No. 04-06-00242a) grants to VMK.