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Sleep and Core Temperature Measures
Following Microinjection of Muscimol
into the Medial Preoptic Area in Rats
Wallace B. Mendelson, Ph.D.
Although benzodiazepines are thought to exert their effects on sleep by altering
GABAergic function, several studies using peripheral administration have pointed to
differences in pharmacologic actions of these compounds and the GABA-A receptor
agonist muscimol. Among the possible explanations for these differences are the notions
that these agents may have very different rates of entry into the central nervous system
(CNS), or that muscimol might be affecting a wide range of GABA receptors throughout
the CNS. One way to test these concerns would be to administer both agents directly into
a localized site. It has previously been observed that triazolam, as well as
nonbenzodiazepine agents such as pentobarbital and ethanol, induce sleep in the rat
when microinjected into the medial preoptic area (MPA). To this end, we have
microinjected muscimol into the MPA of rats, using doses (0.1 g and 1.0 g)
substantially higher than those reported to produce endocrine effects after microinjection
there, and examined the consequent sleep and core temperature. Neither dose of
muscimol significantly differed from vehicle on any measure. Insofar as the current work
involved localized administration, the implication is that differences between
benzodiazepines and muscimol in pharmacologic effects that have been detected after
peripheral administration may not be due to differences in CNS penetrance. Other
possibilities, including differing duration of activation of ion channels or differing actions
on receptors of various subtype composition, are considered. (Sleep and Hypnosis
1999;1:158-162)
| Keywords: muscimol, GABA, sleep, REM sleep, power spectra, benzodiazepines |
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