Changes in rat sleep after single and repeated injections of the long-acting somatostatin analog octreotide.
Somnogenic activity is attributed to both growth hormone (GH) and GH-releasing hormone (GHRH). The aim of our experiments was to study sleep after suppression of the somatotropic axis by means of administration of a long-lasting somatostatin analog, octreotide. Rats received subcutaneous injections of physiological saline (baseline), octreotide (1, 10, and 200 microg/kg), or a control solution just before light onset, and sleep-wake activity and cortical brain temperature were recorded for 23 h. Each dose of octreotide slightly promoted rapid eye movement sleep (REMS) during the 12-h light period. Non-REM sleep (NREMS) was strongly suppressed for 1 h in response to 10 and 200 microg/kg octreotide. This was followed by slight increases in NREMS time and significant enhancements in electroencephalogram slow-wave activity during NREMS after 200 microg/kg octreotide. The octreotide-induced inhibition of the somatotropic axis, as determined by plasma GH levels, vanished by the time sleep increased. Another group of rats received 10 microg/kg octreotide twice a day for 5 days. This treatment elicited persistent decreases in both NREMS time and NREMS intensity. The results support the previously reported REMS-promoting activity of somatostatin in rats. The decreases in sleep after repeated injections of octreotide are attributed to a withdrawal of the normal sleep-promoting activity of GH. The role of GHRH-GH in octreotide-induced acute suppression of NREMS is currently not clear. Other mechanisms, such as mimicking central transmitter functions of somatostatin by octreotide, should also be considered.
Beranek
L
L
Department of Physiology, Szent-Györgyi Medical University, Szeged, Hungary.
Obál
F
F
Taishi
P
P
Bodosi
B
B
Laczi
F
F
Krueger
J M
JM
D000818:Animals; D004334:Drug Administration Schedule; D004569:Electroencephalography; D013006:Growth Hormone / Q000097:blood; D006728:Hormones / Q000008:administration & dosage* / Q000494:pharmacology; D007267:Injections; D008297:Male; D015282:Octreotide / Q000008:administration & dosage* / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012890:Sleep / Q000187:drug effects* / Q000502:physiology; D012894:Sleep Stages / Q000187:drug effects / Q000502:physiology
D006728:Hormones; D013006:Growth Hormone; D015282:Octreotide