Abstract Mkid 26

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.