Enhancement of a diazepam withdrawal symptom by bicuculline and yohimbine

Idemudia, Smart O.; Mathis, Diane A.; Lal, Harbans

doi:10.1016/0028-3908(87)90126-2

Cited by 9 publications

References 21 publications

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Pentylenetetrazole‐like stimulus is produced in rats during withdrawal from ingested chlordiazepoxide

Idemudia

Lal

1989

Drug Development Research

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Idemudia, S.O., and H. Lal: Pentylenetetrazole-like stimulus is produced in rats during withdrawal from ingested chlordiazepoxide. Drug Dev. Res. 16:23-29, 1989.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 mgikg, i.p.) and on the other lever after saline (1 mlikg, 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 15-1 788) 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.

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Pentylenetetrazole‐like stimulus is produced in rats during withdrawal from ingested chlordiazepoxide

Idemudia

Lal

1989

Drug Development Research

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A pentylenetetrazol‐like stimulus during cocaine withdrawal: Blockade by diazepam but not haloperidol

Wood

Laraby

Lal

1989

Drug Development Research

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Wood, D.M., P.R. Laraby, and H. Lal: A pentylenetetrazol-like stimulus during cocaine withdrawal: Blockade by diazepam but not haloperidol. Drug Dev. Res. 16:269-276, 1989. In the present experiment, rats were trained to discriminate the stimulus properties of an anxiogenic drug, pentylenetetrazol (PTZ), 20 mgikg, from saline using a food-rewarded two-lever choice task. Following training: substitution tests were performed, and rats selected the PTZ-appropriate lever after PTZ in a dose-dependent manner. Cocaine (5-20 mgikg) did not substitute for PTZ. Subsequently, testing and training were halted, and cocaine, 20 mgikgi8 hr, was administered to three groups of ten rats per group for 3, 7, and 14 days. Withdrawal from cocaine produced a PTZ-like stimulus that increased in intensity proportionally to the duration of chronic cocaine exposure. The selection of the PTZ lever by these subjects during withdrawal was reversed following administration of diazepam, 5 mgikg, but not by haloperidol, 0.64 mgikg. Stimulus control tests performed 2 weeks following the last withdrawal test demonstrated a return to baseline responding, with no significant loss of stimulus control. These data demonstrate the development of a PTZ-like interoceptive stimulus during withdrawal from cocaine, which suggests the possibility of an anxiety-tike stimulus during cocaine withdrawal. This anxiety-like component appears to be influenced by the duration of cocaine exposure.

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