Intracerebroventricular and locus coeruleus microinjections of somatostatin antagonist decrease REM sleep in rats.
In order to study the role of endogenous somatostatin in the physiologic modulation of REM sleep (REMS), we measured the effect of intracerebroventricular (ICV) injection of somatostatin antagonist (SA) cyclo-(7-aminoheptanoyl-phe-d-trp-lys-thr(bzl)) on sleep in rats. The effect of ICV SA was also tested after 24-h REMS deprivation with the platform method. To study the role of locus coeruleus (LC) as a site of the sleep inducing action for somatostatin and galanin we microinjected SA, somatostatin, and galanin locally into LC. In all experiments, vigilance state was analyzed visually from 6 h post-injection EEG/EMG recording. Injection of 0.5 and 2 nmol of SA ICV reduced spontaneous REMS and 2 nmol dose reduced also rebound REMS after REMS deprivation when compared with controls (artificial cerebrospinal fluid vehicle). Microinjection of 0.25 nmol of SA into LC reduced REMS, whereas microinjection of somatostatin, galanin, and a combined injection of them were not effective to induce REMS. The results suggest that endogenous somatostatin may contribute to facilitation of REMS. Somatostatin receptors in the LC may be one possible mediator of this effect.
Toppila
J
J
Institute of Biomedicine, Department of Physiology, P.O. Box 9, FIN-00014 University of Helsinki, Helsinki, Finland. Jussi.Toppila@helsinki.fi
Niittymäki
P
P
Porkka-Heiskanen
T
T
Stenberg
D
D
D000818:Animals; D004569:Electroencephalography / Q000187:drug effects; D004576:Electromyography / Q000187:drug effects; D019004:Galanin / Q000008:administration & dosage / Q000494:pharmacology; D006727:Hormone Antagonists / Q000494:pharmacology*; D007276:Injections, Intraventricular; D008125:Locus Coeruleus / Q000502:physiology*; D008297:Male; D008845:Microinjections; D051381:Rats; D017208:Rats, Wistar; D012895:Sleep, REM / Q000187:drug effects*; D013004:Somatostatin / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000037:antagonists & inhibitors* / Q000494:pharmacology
D006727:Hormone Antagonists; D013004:Somatostatin; C043820:cyclo(7-aminoheptanoylphenylalanyl-tryptophyl-lysyl-benzylthreonyl); D019004:Galanin