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

Abstract

1. 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 electrochemical signals, within CA 1 region of hippocampus in the freely moving and behaving, male, Sprague Dawley laboratory rat. 2. 2. Concurrently, four parameters of open-field Behavior I.E. Ambulations, Rearing, Fine Movements and Central Ambulatory behavior (a measure of anxiety reduction behavior), were assayed by infrared photobeam detection. 3. 3. Time course studies showed that the mechanism of action of the triazolobenzodiazepine (TBZD), adinazolam, (Deracyn®) is dramatically different from that of the classical benzodiazepine (BZD), diazepam (Valium®) i.e., adinazolam increased, whereas diazepam decreased, 5-HT release within CA 1 region of hippocampus in the freely moving and behaving rat. 4. 4. Adinazolam initially increased NE release and then decreased NE release 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 decrease in NE release produced by diazepam. 5. 5. The Behavioral Activity Patterns, derived from same animal controls, simultaneously with detection of in vivo microvoltammetric signals for NE release and 5-HT release, showed that the BZD, diazepam, exhibited more potent sedative properties than did the TBZD adinazolam. 6. 6. Hippocampal 5-HT and NE release effects of the TBZD, adinazolam, concomitant with behavioral effects lends explanation to the dual anxiolytic/antidepressant properties of the TBZDs.