Effects of parenterally administered triazolam on sleep in rats with lesions of the preoptic area.
In previous work we have reported that microinjections of triazolam or pentobarbital into the medial preoptic area of the anterior hypothalamus produce a hypnotic effect. This finding raised the possibility that the sleep-enhancing actions after systemic administration of these compounds might be mediated by hypnogenic mechanisms in the preoptic area. The current study examined whether sleep enhancement by triazolam requires the anatomic integrity of the preoptic area. Nine rats with histologically confirmed lesions of the preoptic area induced by ibotenic acid (2.5 microg/microl in 0.4 microl), and 10 rats that had undergone a sham lesion procedure, had 2-h sleep studies that confirmed that by day 5 measures of total sleep time and sleep latency had returned to preintervention values. Rats were then given triazolam 0.8 mg/kg or vehicle intraperitoneally in counterbalanced order, on days 7 and 9 postlesion, in an environment with an ambient temperature of 25 degrees C. Following injections at 1000 h, in conditions in which lights were on from 0800-2000 h, 2-h sleep studies were performed. In the lesioned rats, triazolam significantly decreased sleep latency and increased total sleep time, primarily by increasing NREM sleep, whereas injections of vehicle did not. In summary, parenterally administered triazolam was found to have hypnotic effects in rats who were 1 week post-preoptic area lesion. These data are interpreted in light of previous evidence of redundancy of sleep-regulating mechanisms in the nervous system.
Sleep Research Laboratory, The University of Chicago, IL 60637, USA.
W B
WB
Mendelson
D000818:Animals; D018690:Excitatory Amino Acid Agonists / Q000633:toxicity; D006993:Hypnotics and Sedatives / Q000008:administration & dosage / Q000494:pharmacology*; D007051:Ibotenic Acid / Q000633:toxicity; D007274:Injections, Intraperitoneal; D008297:Male; D011301:Preoptic Area / Q000473:pathology / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012890:Sleep / Q000187:drug effects*; D012894:Sleep Stages / Q000187:drug effects; D012895:Sleep, REM / Q000187:drug effects; D014229:Triazolam / Q000008:administration & dosage / Q000494:pharmacology*
D018690:Excitatory Amino Acid Agonists; D006993:Hypnotics and Sedatives; D014229:Triazolam; D007051:Ibotenic Acid