caa a22 4500 605537755 CHVBK 20210128100859.0 cr unu---uuuuu 210128e20150101xx s 000 0 eng 10.1007/s10517-015-2744-9 doi (NATIONALLICENCE)springer-10.1007/s10517-015-2744-9 Peripheral Administration of a μ-Opioid Receptor Agonist DAMGO Suppresses the Anxiolytic and Stimulatory Effects of Caffeine [Elektronische Daten] [S. Sudakov, G. Nazarova, E. Alekseeva, A. Kolpakov] We studied the possibility of modulation of the stimulatory and anxiolytic effects of caffeine by activation of μ-opioid receptors in the gastrointestinal tract. Caffeine in a dose of 10 mg/kg (but not in a dose of 100 mg/kg) had a strong anxiolytic and psychostimulant effect. This effect was manifested in a significant increase in the time spent in the open arms of the elevated plus-maze, elevation of locomotor activity, and stimulation of metabolism. Administration of DAMGO to animals receiving caffeine in a dose of 10 mg/kg abolished the anxiolytic and psychostimulant effects of caffeine. By contrast, administration of DAMGO to rats receiving caffeine in a dose of 100 mg/kg had the anxiolytic effect. Activation of peripheral μ-opioid receptors is followed by the inhibition of the central μ-opioid system. We observed a decrease in the number of μ-opioid receptors in the midbrain and cerebral cortex and inhibition of β-endorphin release from nerve ending of the cingulate cortex in rats. These changes are probably followed by activation of the adenosine system in the brain. Caffeine dose should be increased to achieve the effect. Therefore, the anxiolytic and stimulatory effects of caffeine in a dose of 10 mg/kg are abolished under these conditions. By contrast, the anxiolytic effect of caffeine in a dose of 100 mg/kg (not observed under normal conditions) develops after this treatment. Springer Science+Business Media New York, 2015 caffeine nationallicence locomotor activity nationallicence indirect calorimetry nationallicence elevated plus-maze nationallicence endogenous opioid system nationallicence Sudakov S. P. K. Anokhin Research Institute of Normal Physiology, Moscow, Russia aut Nazarova G. P. K. Anokhin Research Institute of Normal Physiology, Moscow, Russia aut Alekseeva E. P. K. Anokhin Research Institute of Normal Physiology, Moscow, Russia aut Kolpakov A. P. K. Anokhin Research Institute of Normal Physiology, Moscow, Russia aut Bulletin of Experimental Biology and Medicine Springer US; http://www.springer-ny.com 158/3(2015-01-01), 295-297 0007-4888 158:3<295 2015 158 10517 https://doi.org/10.1007/s10517-015-2744-9 text/html Onlinezugriff via DOI BK010053 XK010053 XK010000 Metadata rights reserved Springer special CC-BY-NC licence nationallicence 1 research-article jats NATIONALLICENCE NATIONALLICENCE NL-springer NATIONALLICENCE 856 40 https://doi.org/10.1007/s10517-015-2744-9 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Sudakov S. P. K. Anokhin Research Institute of Normal Physiology, Moscow, Russia aut NATIONALLICENCE 700 1- Nazarova G. P. K. Anokhin Research Institute of Normal Physiology, Moscow, Russia aut NATIONALLICENCE 700 1- Alekseeva E. P. K. Anokhin Research Institute of Normal Physiology, Moscow, Russia aut NATIONALLICENCE 700 1- Kolpakov A. P. K. Anokhin Research Institute of Normal Physiology, Moscow, Russia aut NATIONALLICENCE 773 0- Bulletin of Experimental Biology and Medicine Springer US; http://www.springer-ny.com 158/3(2015-01-01), 295-297 0007-4888 158:3<295 2015 158 10517