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Diazepam alters brain 5-HT function in man: implications for the acute and chronic effects of benzodiazepines

Published online by Cambridge University Press:  09 July 2009

D. J. Nutt*
Affiliation:
University Department of Psychiatry, Warneford Hospital, Oxford and MRC Clinical Pharmacology Unit, Research Unit, Littlemore Hospital, Oxford
P. J. Cowen
Affiliation:
University Department of Psychiatry, Warneford Hospital, Oxford and MRC Clinical Pharmacology Unit, Research Unit, Littlemore Hospital, Oxford
*
1Address for correspondence: Dr D. J. Nutt, National Institute on Alcohol Abuse & Alcoholism, Building 10, Room 3B19, 9000 Rockville Pike, Bethesda, Maryland 20892, USA

Synopsis

The effect of diazepam on brain 5-HT-mediated neuroendocrine responses was studied in healthy male volunteers. An acute dose of diazepam (15 mg) significantly attenuated the prolactin and growth hormone responses to intravenous L-tryptophan. After 3 weeks administration of diazepam (25 mg/d) these responses had returned to normal despite much higher plasma diazepam concentrations, suggesting that tolerance had occurred. A reduction in brain 5-HT function may underlie some of the acute therapeutic actions of benzodiazepines. It is possible that excessive ‘rebound’ 5-HT activity may contribute to the abstinence syndrome seen on benzodiazepine withdrawal.

Type
Research Article
Copyright
Copyright © Cambridge University Press 1987

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