Triazolam suppresses the induction of hippocampal long-term potentiation.
Benzodiazepines are sedative hypnotics that produce marked anterograde amnesia in humans. These pharmacological properties are thought to result from the potentiation of GABA-A receptor function and subsequent attenuation of long-term potentiation (LTP), however many reports have suggested this is not the case for triazolam. Using electrophysiological recordings in a cell line expressing recombinant GABA-A receptors, we confirm that triazolam is an efficacious positive allosteric modulator of GABA-A receptors. Triazolam also slowed the decay of spontaneous inhibitory synaptic currents, reduced the amplitude of fEPSPs elicited during a theta burst and reduced the magnitude of LTP in hippocampal CA1 neurones in vitro. These data show that triazolam modifies LTP induction consistent with an enhancement of GABA-A receptor function via activation of the allosteric benzodiazepine-site.
Maubach
Karen A
KA
Molecular and Cellular Neuroscience, Merck Sharp and Dohme Research Laboratories, Terlings Park, Harlow, Essex, CM20 2QR, UK. karen_maubach@merck.com
Martin
Karine
K
Choudhury
Hedaythul I
HI
Seabrook
Guy R
GR
D000818:Animals; D004305:Dose-Response Relationship, Drug; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D058785:GABA-A Receptor Agonists; D006624:Hippocampus / Q000187:drug effects* / Q000502:physiology; D006801:Humans; D017774:Long-Term Potentiation / Q000187:drug effects* / Q000502:physiology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D051381:Rats; D017207:Rats, Sprague-Dawley; D011963:Receptors, GABA-A / Q000502:physiology; D014229:Triazolam / Q000494:pharmacology*
D018691:Excitatory Amino Acid Antagonists; D058785:GABA-A Receptor Agonists; D011963:Receptors, GABA-A; D014229:Triazolam