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Science 14 July 1972:
Vol. 177. no. 4044, pp. 180 - 183
DOI: 10.1126/science.177.4044.180
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Articles

Benzodiazepines: Anxiety-Reducing Activity by Reduction of Serotonin Turnover in the Brain

C. David Wise 1, Barry D. Berger 1, and Larry Stein 1

1 Wyeth Laboratories, Philadelphia, Pennsylvania 19101

The anxiety-reducing effects of minor tranquilizers in the rat conflict test were mimicked by serotonin antagonists and by p-chlorophenylalanine, an inhibitor of serotonin synthesis; the depressant effects of the minor tranquilizers were mimicked by norepinephrine antagonists. Intraventricular injections of serotonin led to a suppression of behavior, and also antagonized the anxiety-reducing action of benzodiazeprines. Intraventricular injections of norepinephrine led to a release of punished behavior from suppression, and also antagonized the depressant action of benzodiazepines. The anxiety-reducing activity, and the decrease in serotonin turnover induced by benzodiazepines, were maintained over repeated doses, whereas depressant activity, and the decrease induced in norepinephrine turnover, both rapidly underwent tolerance. Tranquilizers may exert their anxiety-reducing effects by a reduction of serotonin activity in a behaviorally suppressive punishment system, and they may exert their depressant effects by a reduction of norepinephrine activity in a behaviorally facilitatory reward system.


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