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Differential tolerance to the effects of chlordiazepoxide on unpunished and punished operant responding following chronic treatment
Journal article   Open access   Peer reviewed

Differential tolerance to the effects of chlordiazepoxide on unpunished and punished operant responding following chronic treatment

Jed S. Shumsky and Irwin Lucki
Pharmacology, biochemistry and behavior, v 53(3), pp 593-601
01 Mar 1996
PMID: 8866960
url
https://doi.org/10.1016/0091-3057(95)02056-XView
Published, Version of Record (VoR) Open

Abstract

Benzodiazepine Chlordiazepoxide Conflict responding Rat Tolerance Withdrawal
Differential development of tolerance to the effects of benzodiazepines (BZs) is a common clinical phenomenon. To examine whether the development of tolerance to the response-suppressant and antipunishment effects of BZs were differentially regulated in animals, male Sprague-Dawley rats were treated chronically with either the BZ receptor agonist Chlordiazepoxide (CDP, 25 mg/kg, IP b.i.d.) or saline for 15 weeks and examined under a multiple schedule of operant behavior. Chronic administration of CDP produced tolerance to its suppressive effects on unpunished responding (RI 80 s) but no tolerance to its enhancing effects on punished responding. This conclusion is supported by three observations. First, repeated priming with CDP produced tolerance to its response-suppressive effects in the RI 80-s schedule and revealed increases in punished responding. Second, baseline levels for punished responding remained elevated over the 15-week treatment period. Third, tolerance developed to the response-suppressant effects of CDP under the RI 80-s schedule, as indicated by a sixfold shift to the right in the dose-response curves for rats treated chronically with CDP when compared to saline-treated controls. However, tolerance did not develop to the antipunishment effects of CDP, as indicated by no differences in the dose-response curves for punished responding. Discontinuation of chronic treatment disrupted unpunished responding only on the first day, and reversed the increase in punished responding. Taken together, these results indicate that differential regulation occurs for the development of tolerance to the response-suppressant and antipunishment effects of BZs.

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Collaboration types
Domestic collaboration
Web of Science research areas
Behavioral Sciences
Neurosciences
Pharmacology & Pharmacy
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