MECHANISM OF TRIAZOLO-BENZODIAZEPINE AND BENZODIAZEPINE ACTION IN ANXIETY AND DEPRESSION - BEHAVIORAL-STUDIES WITH CONCOMITANT IN-VIVO CA(1) HIPPOCAMPAL NOREPINEPHRINE AND SEROTONIN RELEASE DETECTION IN THE BEHAVING ANIMAL

1. Real time, in vivo microvoltammetric studies were performed, using miniature carbon-based sensors, to concurrently detect norepinephrine (NE) release and serotonin (5-HT) release, in 2 separate electrochemic al signals, within CA(1) region of hippocampus in the freely moving an d behaving, male, Sprague Dawley laboratory rat. 2. Concurrently, four parameters of open-field behavior, i.e. Ambulations, Rearing, Fine Mo vements and Central Ambulatory behavior (a measure of anxiety reductio n behavior), were assayed by infrared photobeam detection. 3. Time cou rse studies showed that the mechanism of action of the triazolobenzodi azepine (TBZD), adinazolam, (Deracyn(R)) is dramatically different fro m that of the classical benzodiazepine (BZD), diazepam (Valium(R)), i. e., adinazolam increased, whereas diazepam decreased, 5-HT release wit hin CA(1) region of hippocampus in the freely moving and behaving rat. 4. Adinazolam initially increased NE release and then decreased NE re lease in CA(1) region of hippocampus in the freely moving and behaving rat whereas diazepam only decreased the electrochemical signal for NE ; the decrease in NE produced by adinazolam was greater than the decre ase in NE release produced by diazepam. 5. The Behavioral Activity Pat terns, derived from same animal controls, simultaneously with detectio n of in vivo microvoltammetric signals for NE release and 5-HT release , showed that the BZD,diazepam, exhibited more potent sedative propert ies than did the TBZD adinazolam. 6. Hippocampal 5-HT and NE release e ffects of the TBZD, adinazolam, concomitant with behavioral effects le nds explanation to the dual anxiolytic/antidepressant properties of th e TBZDs.