Behavioral effects of flunitrazepam: reinforcing and discriminative stimulus effects in rhesus monkeys and prevention of withdrawal signs in pentobarbital-dependent rats

Lisa R Gerak, William L. Woolverton, Michael A. Nader, Graham A. Patrick, Louis S. Harris, Gail Winger, James H. Woods, Charles P France

Research output: Contribution to journalArticle

5 Citations (Scopus)

Abstract

Flunitrazepam was evaluated in several procedures that have been used extensively to study the behavioral effects and abuse potential of positive GABAA modulators. One group of monkeys (n=3) responded to receive injections of methohexital or saline (i.v.) while other groups (n=2-4/group) discriminated vehicle from either pentobarbital or triazolam. Other monkeys (n=2) received diazepam daily and discriminated flumazenil from vehicle. Finally, the ability of flunitrazepam to prevent the emergence of withdrawal signs in pentobarbital-treated rats was evaluated. Flunitrazepam maintained i.v. self-administration that was, on average, less than that maintained by methohexital and greater than that maintained by saline. In drug discrimination studies, flunitrazepam substituted for pentobarbital and for triazolam and failed to substitute for flumazenil. In rats (n=3-6/group), signs of withdrawal were not evident when flunitrazepam treatment replaced pentobarbital treatment; withdrawal signs emerged when either pentobarbital or flunitrazepam treatment was terminated. Taken together with data from previous studies, these data suggest that the abuse liability of flunitrazepam is comparable to that of other benzodiazepines.

Original languageEnglish (US)
Pages (from-to)39-49
Number of pages11
JournalDrug and Alcohol Dependence
Volume63
Issue number1
DOIs
StatePublished - Jun 1 2001

Fingerprint

Flunitrazepam
Pentobarbital
Macaca mulatta
withdrawal
Rats
stimulus
Methohexital
Triazolam
abuse
Group
Flumazenil
self-administration
Haplorhini
liability
discrimination
Self Administration
drug
Diazepam
Benzodiazepines
ability

Keywords

  • Drug discrimination
  • Flunitrazepam
  • Pentobarbital-dependent rats
  • Rhesus monkey
  • Self-administration

ASJC Scopus subject areas

  • Medicine(all)
  • Behavioral Neuroscience
  • Toxicology
  • Health(social science)

Cite this

Behavioral effects of flunitrazepam : reinforcing and discriminative stimulus effects in rhesus monkeys and prevention of withdrawal signs in pentobarbital-dependent rats. / Gerak, Lisa R; Woolverton, William L.; Nader, Michael A.; Patrick, Graham A.; Harris, Louis S.; Winger, Gail; Woods, James H.; France, Charles P.

In: Drug and Alcohol Dependence, Vol. 63, No. 1, 01.06.2001, p. 39-49.

Research output: Contribution to journalArticle

Gerak, Lisa R ; Woolverton, William L. ; Nader, Michael A. ; Patrick, Graham A. ; Harris, Louis S. ; Winger, Gail ; Woods, James H. ; France, Charles P. / Behavioral effects of flunitrazepam : reinforcing and discriminative stimulus effects in rhesus monkeys and prevention of withdrawal signs in pentobarbital-dependent rats. In: Drug and Alcohol Dependence. 2001 ; Vol. 63, No. 1. pp. 39-49.
@article{d06ce8a1b0a64f85b4b7e3e96b2d4898,
title = "Behavioral effects of flunitrazepam: reinforcing and discriminative stimulus effects in rhesus monkeys and prevention of withdrawal signs in pentobarbital-dependent rats",
abstract = "Flunitrazepam was evaluated in several procedures that have been used extensively to study the behavioral effects and abuse potential of positive GABAA modulators. One group of monkeys (n=3) responded to receive injections of methohexital or saline (i.v.) while other groups (n=2-4/group) discriminated vehicle from either pentobarbital or triazolam. Other monkeys (n=2) received diazepam daily and discriminated flumazenil from vehicle. Finally, the ability of flunitrazepam to prevent the emergence of withdrawal signs in pentobarbital-treated rats was evaluated. Flunitrazepam maintained i.v. self-administration that was, on average, less than that maintained by methohexital and greater than that maintained by saline. In drug discrimination studies, flunitrazepam substituted for pentobarbital and for triazolam and failed to substitute for flumazenil. In rats (n=3-6/group), signs of withdrawal were not evident when flunitrazepam treatment replaced pentobarbital treatment; withdrawal signs emerged when either pentobarbital or flunitrazepam treatment was terminated. Taken together with data from previous studies, these data suggest that the abuse liability of flunitrazepam is comparable to that of other benzodiazepines.",
keywords = "Drug discrimination, Flunitrazepam, Pentobarbital-dependent rats, Rhesus monkey, Self-administration",
author = "Gerak, {Lisa R} and Woolverton, {William L.} and Nader, {Michael A.} and Patrick, {Graham A.} and Harris, {Louis S.} and Gail Winger and Woods, {James H.} and France, {Charles P}",
year = "2001",
month = "6",
day = "1",
doi = "10.1016/S0376-8716(00)00189-7",
language = "English (US)",
volume = "63",
pages = "39--49",
journal = "Drug and Alcohol Dependence",
issn = "0376-8716",
publisher = "Elsevier Ireland Ltd",
number = "1",

}

TY - JOUR

T1 - Behavioral effects of flunitrazepam

T2 - reinforcing and discriminative stimulus effects in rhesus monkeys and prevention of withdrawal signs in pentobarbital-dependent rats

AU - Gerak, Lisa R

AU - Woolverton, William L.

AU - Nader, Michael A.

AU - Patrick, Graham A.

AU - Harris, Louis S.

AU - Winger, Gail

AU - Woods, James H.

AU - France, Charles P

PY - 2001/6/1

Y1 - 2001/6/1

N2 - Flunitrazepam was evaluated in several procedures that have been used extensively to study the behavioral effects and abuse potential of positive GABAA modulators. One group of monkeys (n=3) responded to receive injections of methohexital or saline (i.v.) while other groups (n=2-4/group) discriminated vehicle from either pentobarbital or triazolam. Other monkeys (n=2) received diazepam daily and discriminated flumazenil from vehicle. Finally, the ability of flunitrazepam to prevent the emergence of withdrawal signs in pentobarbital-treated rats was evaluated. Flunitrazepam maintained i.v. self-administration that was, on average, less than that maintained by methohexital and greater than that maintained by saline. In drug discrimination studies, flunitrazepam substituted for pentobarbital and for triazolam and failed to substitute for flumazenil. In rats (n=3-6/group), signs of withdrawal were not evident when flunitrazepam treatment replaced pentobarbital treatment; withdrawal signs emerged when either pentobarbital or flunitrazepam treatment was terminated. Taken together with data from previous studies, these data suggest that the abuse liability of flunitrazepam is comparable to that of other benzodiazepines.

AB - Flunitrazepam was evaluated in several procedures that have been used extensively to study the behavioral effects and abuse potential of positive GABAA modulators. One group of monkeys (n=3) responded to receive injections of methohexital or saline (i.v.) while other groups (n=2-4/group) discriminated vehicle from either pentobarbital or triazolam. Other monkeys (n=2) received diazepam daily and discriminated flumazenil from vehicle. Finally, the ability of flunitrazepam to prevent the emergence of withdrawal signs in pentobarbital-treated rats was evaluated. Flunitrazepam maintained i.v. self-administration that was, on average, less than that maintained by methohexital and greater than that maintained by saline. In drug discrimination studies, flunitrazepam substituted for pentobarbital and for triazolam and failed to substitute for flumazenil. In rats (n=3-6/group), signs of withdrawal were not evident when flunitrazepam treatment replaced pentobarbital treatment; withdrawal signs emerged when either pentobarbital or flunitrazepam treatment was terminated. Taken together with data from previous studies, these data suggest that the abuse liability of flunitrazepam is comparable to that of other benzodiazepines.

KW - Drug discrimination

KW - Flunitrazepam

KW - Pentobarbital-dependent rats

KW - Rhesus monkey

KW - Self-administration

UR - http://www.scopus.com/inward/record.url?scp=0035372507&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0035372507&partnerID=8YFLogxK

U2 - 10.1016/S0376-8716(00)00189-7

DO - 10.1016/S0376-8716(00)00189-7

M3 - Article

C2 - 11297830

AN - SCOPUS:0035372507

VL - 63

SP - 39

EP - 49

JO - Drug and Alcohol Dependence

JF - Drug and Alcohol Dependence

SN - 0376-8716

IS - 1

ER -