Increased sensitivity to benzodiazepine antagonists in rats following chronic treatment with a low dose of diazepam

  title={Increased sensitivity to benzodiazepine antagonists in rats following chronic treatment with a low dose of diazepam},
  author={Irwin Lucki and Robert F. Kucharik},
The effects of benzodiazepine (BZ) antagonists on operant behavior were examined in rats chronically administered a low dose of diazepam (DZ). The low maintenance dose of DZ (5 mg/kg twice daily) was selected as more closely associated with its anxiolytic effects than the higher treatment doses previously used to study BZ dependence. Food-restricted rats were trained to press a lever for food reinforcement under a FR20 schedule of reinforcement prior to the start of DZ administration. Acute… Expand
Effects of the 5-HT3 antagonist ondansetron on benzodiazepine-induced operant behavioural dependence in rats
It is demonstrated for the first time that it is possible to use operant procedures to detect spontaneous BZ withdrawal, and it is suggested that 5-HT3 antagonists may have relatively limited utility in treating some signs of BZ dependence. Expand
Tolerance, cross-tolerance and dependence measured by operant responding in rats treated with triazolam via osmotic pumps
Differences between compounds highlighted with this model are in agreement with previous observations that these agents possess different pharmacological profiles and different potentials to induce tolerance and dependence. Expand


Withdrawal from diazepam substitutes for the discriminative stimulus properties of pentylenetetrazol.
Results suggest that PTZ discrimination provides a sensitive, stable assay for the detection of withdrawal from benzodiazepine dependence. Expand
Behavioral effects of benzodiazepine antagonists in chlordiazepoxide tolerant and non-tolerant rats.
Differences in mechanism of action of antagonists in tolerance and non-tolerant subjects are suggested, and the sensitivity that is induced to antagonists in tolerant subjects is not conferred equally to all drugs having benzodiazepine antagonist activity. Expand
Disruption of schedule-controlled behavior by Ro 15-1788 one day after acute treatment with benzodiazepines
The results show that Ro 15-1788 can precipitate disruption of schedule-controlled behavior 1 day after acute treatment with benzodiazepines. Expand
The pentylenetetrazol model of anxiety detects withdrawal from diazepam in rats.
Data indicate that animals trained to discriminate a PTZ cues generalize the benzodiazepine withdrawal state to the PTZ cue, and discriminate the withdrawal state for long periods of time, agreeing with clinical observations of long-lasting anxiety signs during benzodiazine withdrawal. Expand
Investigation of the actions of the benzodiazepine antagonists Ro 15-1788 and CGS 8216 using the schedule-controlled behavior of rats
  • D. Sanger
  • Medicine, Psychology
  • Pharmacology Biochemistry and Behavior
  • 1986
Diazepam and zolpidem produced dose-related decreases in rates of food-reinforced lever-pressing maintained by a fixed-ratio (FR 10) schedule but neither diazepam nor zolPidem blocked the rate reducing effect of CGS 8216 which may not be due to an action at benzodiazepine receptors. Expand
Bidirectional effects of chronic treatment with agonists and inverse agonists at the benzodiazepine receptor
Repeated administration of benzodiazepine agonists, sufficient to cause tolerance to their pharmacological actions and to those of beta-carboline agonist, increased all of the effects of the partial inverse agonist and some of the actions of the full inverse agonists. Expand
Precipitated diazepam withdrawal in baboons: effects of dose and duration of diazepam exposure.
It is suggested that benzodiazepines produce meaningful functional changes in the central nervous system after exposure to relatively low doses and after relatively short durations of exposure. Expand
Benzodiazepine dependence in mice after ingestion of drug-containing food pellets.
This technique provides a quantitative method to study the effect of withdrawal from benzodiazepines in mice by measuring changes in body tone, abdominal tone and pupil size during abstinence. Expand
CGS 8216: agonist and diazepam-antagonist effects in rodents.
  • H. Shannon, N. Katzman
  • Chemistry, Medicine
  • The Journal of pharmacology and experimental therapeutics
  • 1986
CGS 8216, a pyrazoloquinolinone benzodiazepine receptor ligand, was administered alone and concomitantly with diazepam in order to assess its agonist and diazepam-antagonist properties on severalExpand
Persistent reversal of tolerance to anticonvulsant effects and GABAergic subsensitivity by a single exposure to benzodiazepine antagonist during chronic benzodiazepine administration.
Investigation of the time course for antagonist-induced alterations in iontophoretic sensitivity to gamma-aminobutyric acid on dorsal raphe neurons and the re-emergence of anticonvulsant efficacy to bicuculline-induced seizures found persistence of tolerance appears to persist for up to 7 days after a single exposure to benzodiazepine antagonists. Expand