Locomotor responses to benzodiazepines, barbiturates and ethanol in diazepam-sensitive (DS) and -resistant (DR) mice.

Abstract:

:Diazepam-sensitive (DS) and -resistant (DR) mice were selectively bred for increased and reduced sensitivity to the ataxic effects of diazepam (40 mg/kg). Other response differences between DS and DR mice may reflect pleiotropic effects of the genes fixed during their selection. These mice were tested for their sensitivity to the locomotor stimulant effects of several doses of diazepam, flunitrazepam, pentobarbital, phenobarbital, and ethanol. DR mice were more sensitive than DS mice to the locomotor stimulant effects of all drugs except phenobarbital. These results largely support the hypothesis that a common biological mechanism mediates sensitivity to the stimulant effects of sedative-hypnotic drugs. Receptor mediation of the benzodiazepine effects was examined by administering the benzodiazepine receptor antagonist, RO15-1788. Locomotor depression produced by diazepam and flunitrazepam in DS mice was blocked by RO15-1788. However, while the locomotor stimulation produced by diazepam in DR mice was antagonized, the stimulant effect of flunitrazepam was not. This suggests that binding of flunitrazepam to the GABAA-benzodiazepine receptor is not necessary for production of locomotor stimulation.

journal_title

Psychopharmacology

authors

Phillips TJ,Gallaher EJ

doi

10.1007/BF02244976

subject

Has Abstract

pub_date

1992-01-01 00:00:00

pages

125-31

issue

1

eissn

0033-3158

issn

1432-2072

journal_volume

107

pub_type

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