Sleep-inducing effects of adenosine microinjections into the medial preoptic area are blocked by flumazenil.
Microinjection of a wide range of sedative agents, including triazolam, pentobarbital, ethanol and adenosine, into the medial preoptic area has been shown to increase sleep, suggesting that it is an important (though not necessarily the only) anatomic site mediating hypnotic effects of these compounds. The mechanism by which adenosine increases sleep at this site is not clear, but one possibility is that this is related to its effects on the GABA(A)-benzodiazepine receptor complex. In order to assess this possibility, this paper describes the administration of adenosine, alone and in combination with the benzodiazepine receptor blocker flumazenil, into the MPA. It was found that 12.5 and 25 nM of adenosine significantly reduced sleep latency and increased total sleep time. The sleep-inducing effect was blocked by flumazenil. Flumazenil caused a modest increase in total sleep, and prevented the increase in total sleep induced by the higher dose of adenosine. These data suggest that at least one aspect of the hypnotic properties of adenosine is mediated by a direct or indirect action on the GABA(A)-benzodiazepine receptor complex.
Mendelson
W B
WB
Department of Psychiatry, University of Chicago, IL, 60637 USA. wmendels@yoda.bsd.uchicago.edu
D000241:Adenosine / Q000494:pharmacology*; D000700:Analgesics / Q000494:pharmacology*; D000818:Animals; D004347:Drug Interactions; D005442:Flumazenil / Q000494:pharmacology*; D018757:GABA Modulators / Q000494:pharmacology*; D058787:GABA-A Receptor Antagonists; D008297:Male; D008845:Microinjections; D011301:Preoptic Area / Q000737:chemistry / Q000187:drug effects* / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012890:Sleep / Q000187:drug effects*
D000700:Analgesics; D018757:GABA Modulators; D058787:GABA-A Receptor Antagonists; D005442:Flumazenil; D000241:Adenosine