Anxiolytic effect of midazolam microinjected into the dorsal periaqueductal grey area of rats.
In order to investigate the role of the dorsal periaqueductal grey (DPAG) area in the anxiolytic effect of benzodiazepines male Wistar rats (N = 10), weighing 200-250 g at the time of surgery, were microinjected into this structure with midazolam (80 nmol) and submitted to the elevated plus-maze, an ethologically based model of anxiety. Midazolam significantly increased the percentage of open arm entries from 32.4 +/- 4.6 (control) to 49.5 +/- 3.0 and of time spent in the open arms from 21.0 +/- 4.5 (control) to 35.6 +/- 4.8 without affecting the total number of entries into either open or enclosed arms. This effect typifies an anxiolytic effect in the test and was antagonized by the benzodiazepine receptor antagonist flumazenil (80 nmol) microinjected into the same site 10 min before the midazolam (80 nmol) microinjection. Microinjection of flumazenil alone had no effect. These results provide additional evidence for the participation of the DPAG in the physiopathology of anxiety and suggest that it may be a site for the anxiolytic effect of systemically injected benzodiazepines.
Russo
A S
AS
Laboratório de Psicobiologia, Faculdade de Filosofia, Ciências e Letras de Ribeirão Preto, Universidade de São Paulo, Brasil.
Guimarães
F S
FS
De Aguiar
J C
JC
Graeff
F G
FG
D000704:Analysis of Variance; D000818:Animals; D001007:Anxiety / Q000139:chemically induced*; D001522:Behavior, Animal / Q000187:drug effects*; D004357:Drug Synergism; D004558:Electric Stimulation; D005442:Flumazenil / Q000008:administration & dosage / Q000494:pharmacology; D008297:Male; D008845:Microinjections; D008874:Midazolam / Q000008:administration & dosage / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D010487:Periaqueductal Gray / Q000187:drug effects* / Q000502:physiology; D051381:Rats; D011919:Rats, Inbred Strains
D005442:Flumazenil; D008874:Midazolam