Midazolam cue in rats: effects of Ro 15-1788 and picrotoxin.

Abstract:

:The discriminative stimulus effect of midazolam, a short-acting benzodiazepine, was used for testing the effects of drugs thought to act as antagonists at different sites in the proposed benzodiazepine receptor complex. Rats were trained in a standard two-bar operant conditioning procedure with food reinforcers delivered on a tandem schedule. The 0.4 mg/kg dose of midazolam used for training was well discriminated, typically yielding at least 95% correct responding. The benzodiazepine receptor antagonist Ro 15-1788 blocked the discriminative effect of midazolam but did not influence generalization to pentobarbitone (7.5 mg/kg). The indirect GABA antagonist picrotoxin attenuated both generalization to pentobarbitone and its response rate-reducing effect. Picrotoxin had no effect on the discriminative effect of midazolam at 0.4 mg/kg but it blocked the effect of 0.1 mg/kg. Even in doses which reduced overall response rates, nicotine did not block discrimination of midazolam (0.4 mg/kg). The results are consistent with models which postulate a GABA-linked ion channel which is a site of action for barbiturates and which is "downstream" of the benzodiazepine receptor itself.

journal_title

Psychopharmacology

authors

Stolerman IP,Garcha HS,Rose IC

doi

10.1007/BF00310626

subject

Has Abstract

pub_date

1986-01-01 00:00:00

pages

183-8

issue

2

eissn

0033-3158

issn

1432-2072

journal_volume

89

pub_type

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