title: Sustained inhibition of brotizolam induced anterograde amnesia by norharmane and retrograde amnesia by L-glutamic acid in mice.
abstract: Benzodiazepines such as diazepam, lorazepam, are reported to produce anterograde amnesia but these do not affect the retrieval mechanism. Triazodiazepines such as alprazolam, triazolam and brotizolam produce both anterograde and retrograde amnesia. Because benzodiazepine receptor antagonists are known to reverse anterograde amnesia, we wanted to test if inverse agonist can also improve learning and memory. The present study was designed to investigate the effect of norharmane (benzodiazepine receptor inverse agonist) and L-glutamic acid (glutamate receptor agonist) on brotizolam induced anterograde and retrograde amnesia using Morris water maze task in mice. Norharmane reversed anterograde amnesia induced by brotizolam and did not reverse retrograde amnesia induced by it. L-Glutamic acid attenuated retrograde amnesia but did not affect anterograde amnesia induced by brotizolam. These results provide an opportunity to understand the mechanisms of anterograde and retrograde amnesia which may occur with interaction of presynaptic molecules or LTP modulation.
authors.affiliation: Department of Neurology, Post Graduate Institute of Medical Education and Research, Sector-12, Chandigarh 160012, India. akshay@neurologypgi.com
authors.forename: Akshay
authors.initials: A
authors.lastname: Anand
authors.forename: Manish Kumar
authors.initials: MK
authors.lastname: Saraf
authors.forename: Sudesh
authors.initials: S
authors.lastname: Prabhakar
mesh_terms: D020324:Amnesia, Anterograde / Q000139:chemically induced / Q000188:drug therapy*; D000648:Amnesia, Retrograde / Q000139:chemically induced / Q000188:drug therapy*; D000704:Analysis of Variance; D000818:Animals; D001362:Avoidance Learning / Q000187:drug effects; D001381:Azepines / Q000627:therapeutic use*; D001522:Behavior, Animal / Q000187:drug effects; D002243:Carbolines; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D005260:Female; D018698:Glutamic Acid; D006247:Harmine / Q000031:analogs & derivatives; D006993:Hypnotics and Sedatives / Q000627:therapeutic use*; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D051379:Mice; D011930:Reaction Time / Q000187:drug effects / Q000502:physiology
chemical_list: D001381:Azepines; D002243:Carbolines; D006993:Hypnotics and Sedatives; D018698:Glutamic Acid; D006247:Harmine; C020960:brotizolam; C010262:norharman