QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

HOME  |   SEARCH  |   ARCHIVE  |   SUBSCRIBE  |   CONTACT  |   HELP

This Article Full Text Full Text (PDF) Submit an eLetter Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Web of Science (63) Citing Articles via Google Scholar Google Scholar Articles by Gonzalez, L. E. Articles by File, S. E. Search for Related Content PubMed PubMed Citation Articles by Gonzalez, L. E. Articles by File, S. E.

 Previous Article  |  Next Article 

Volume 17, Number 4, Issue of February 15, 1997 pp. 1505-1511
Copyright ©1997 Society for Neuroscience

A Five Minute Experience in the Elevated Plus-Maze Alters the State of the Benzodiazepine Receptor in the Dorsal Raphe Nucleus

Received Oct. 3, 1996; revised Nov. 27, 1996; accepted Dec. 2, 1996.

Luis E. Gonzalez and Sandra E. File

Psychopharmacology Research Unit, UMDS Division of Pharmacology, Guy's Hospital, London SE1 9RT, United Kingdom

A single 5 min exposure to the elevated plus-maze test of anxiety renders animals insensitive to the anxiolytic effects of the benzodiazepines in this test. The purpose of the present experiments was to explore whether this phenomenon resulted from a change in the functional state of benzodiazepine receptors in the dorsal raphe nucleus. The benzodiazepine receptor agonist midazolam (0.5, 1, and 2 µg) and antagonist flumazenil (100 and 500 ng) were directly administered to the dorsal raphe nucleus in rats either naive to, or with one previous 5 min exposure of, the elevated plus-maze. In naive rats, midazolam produced significant anxiolytic effects at all doses, and flumazenil was silent. In plus-maze-experienced rats, midazolam no longer had anxiolytic effects in the plus-maze, but flumazenil did, indicating that the previous experience of the maze had changed the state of the benzodiazepine receptor. This changed receptor function generalized to the social interaction test. Thus, in naive animals tested in high light, midazolam (0.5, 1, and 2 µg) had significant anxiolytic effects and flumazenil (100 and 500 ng) was silent, whereas in plus-maze-experienced rats both midazolam (1 µg) and flumazenil (500 ng) had significant anxiolytic effects. Extensive analysis of locomotor activity in both tests showed that the changed responsivity to midazolam could not be explained by habituation, because on none of the measures used was there any difference in motor activity scores between plus-maze-naive and experienced rats.

Key words: benzodiazepine receptors; dorsal raphe; midazolam; flumazenil; plus-maze; social interaction

Home  |   Search  |   Archive  |   Subscribe  |   Contact  |   Help