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Pentylenetetrazole‐like stimulus is produced in rats during withdrawal from ingested chlordiazepoxide
Author(s) -
Idemudia Smart O.,
Lal Harbans
Publication year - 1989
Publication title -
drug development research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.582
H-Index - 60
eISSN - 1098-2299
pISSN - 0272-4391
DOI - 10.1002/ddr.430160104
Subject(s) - chlordiazepoxide , flumazenil , saline , benzodiazepine , anxiogenic , pharmacology , lever , anesthesia , phenobarbital , stimulus (psychology) , diazepam , stimulus control , medicine , psychology , anxiolytic , receptor , nicotine , physics , quantum mechanics , psychotherapist
The present study was undertaken to determine whether withdrawal from chlordiazepoxide administered via a liquid diet would produce a pentylenetetrazole (PTZ)‐like stimulus. Rats were trained with food reward in a two‐lever operant task. Presses on one lever were reinforced after injections of PTZ (20 mg/kg, i.p.) and on the other lever after saline (1 ml/kg, i.p.). After rats had acquired the PTZ discrimination, training was halted, and chlordiazepoxide (240 mg/kg/day) was administered via a nutritionally balanced liquid diet to three groups of rats for 3, 4, or 6 days. Upon termination of chronic administration, withdrawal was precipitated with the benzodiazepine receptor blocker flumazenil (Ro 15‐1788) given intraperitoneally. During precipitated withdrawal, the rats selected the PTZ‐appropriate lever, indicating the presence of a PTZ‐like stimulus, and this stimulus was blocked by phenobarbital (80 mg/kg, i.p.). The percentage of rats selecting the PTZ‐appropriate lever depended on the duration of chlordiazepoxide treatment and dose of flumazenil. At 10 days after the last chlordiazepoxide dose, the rats had recovered baseline discrimination, as indicated by their selection of the saline appropriate lever following saline injections and the PTZ‐appropriate lever following PTZ. These data indicate that a subjective effect of withdrawal similar to that produced by the anxiogenic drug PTZ is present during withdrawal from oral chlordiazepoxide.