Evidence map›Paper›PMID 24695241›Full record

ArticleBrain research bulletin2014

Duration of treatment and activation of α1-containing GABAA receptors variably affect the level of anxiety and seizure susceptibility after diazepam withdrawal in rats.

Jovana Kovačević, Tamara Timić, Veera V Tiruveedhula, Bojan Batinić, Ojas A Namjoshi, Marija Milić, Srđan Joksimović, James M Cook, Miroslav M Savić

Open access · bronzeAbstract read
In one paragraph

Article in Brain research bulletin, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing papers in PubMed
0.8field-weighted citation impact, top 33% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

4 citing papers in PubMed, 14 citations in OpenAlex.

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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

9 authors at 2 institutions in 2 countries.

Jovana KovačevićDepartment of Pharmacology, Faculty of Pharmacy, University of Belgrade, Vojvode Stepe 450, 11221 Belgrade, Serbia.
Tamara TimićDepartment of Pharmacology, Faculty of Pharmacy, University of Belgrade, Vojvode Stepe 450, 11221 Belgrade, Serbia.
Veera V TiruveedhulaDepartment of Chemistry and Biochemistry, University of Wisconsin-Milwaukee, P.O. Box 413, Milwaukee, WI 53201, USA.
Bojan BatinićDepartment of Pharmacology, Faculty of Pharmacy, University of Belgrade, Vojvode Stepe 450, 11221 Belgrade, Serbia.
Ojas A NamjoshiDepartment of Chemistry and Biochemistry, University of Wisconsin-Milwaukee, P.O. Box 413, Milwaukee, WI 53201, USA.
Marija MilićDepartment of Pharmacology, Faculty of Pharmacy, University of Belgrade, Vojvode Stepe 450, 11221 Belgrade, Serbia.
Srđan JoksimovićDepartment of Pharmacology, Faculty of Pharmacy, University of Belgrade, Vojvode Stepe 450, 11221 Belgrade, Serbia.
James M CookDepartment of Chemistry and Biochemistry, University of Wisconsin-Milwaukee, P.O. Box 413, Milwaukee, WI 53201, USA.
Miroslav M SavićDepartment of Pharmacology, Faculty of Pharmacy, University of Belgrade, Vojvode Stepe 450, 11221 Belgrade, Serbia. Electronic address: miroslav@pharmacy.bg.ac.rs.
University of Belgrade · RSUniversity of Wisconsin–Milwaukee · US

Funding

Development of new drugs for asthma by targeting GABA(A) receptors in the lungR01HL118561 · NHLBI · UNIVERSITY OF WISCONSIN MILWAUKEE · PI COOK, JAMES M · 2014 to 2017
$2.0M
Design of New Therapeutic Agents to Treat SchizophreniaR01MH096463 · NIMH · UNIVERSITY OF WISCONSIN MILWAUKEE · PI COOK, JAMES M · 2013 to 2017
$1.9M
Synthesis of Alpha2/Alpha3 GABA Agonists to Treat Neuropathic PainR01NS076517 · NINDS · UNIVERSITY OF WISCONSIN MILWAUKEE · PI COOK, JAMES M · 2012 to 2015
$1.3M
NHLBI NIH HHS R01 HL118561NIMH NIH HHS R01 MH096463NINDS NIH HHS R01 NS076517
6 · The paper itself

Abstract

Long-term use of benzodiazepine-type drugs may lead to physical dependence, manifested by withdrawal syndrome after abrupt cessation of treatment. The aim of the present study was to investigate the influence of duration of treatment, as well as the role of α1-containing GABAA receptors, in development of physical dependence to diazepam, assessed through the level of anxiety and susceptibility to pentylenetetrazole (PTZ)-induced seizures, 24h after withdrawal from protracted treatment in rats. Withdrawal of 2mg/kg diazepam after 28, but not after 14 or 21 days of administration led to an anxiety-like behavior in the elevated plus maze. Antagonism of the diazepam effects at α1-containing GABAA receptors, achieved by daily administration of the neutral modulator βCCt (5mg/kg), did not affect the anxiety level during withdrawal. An increased susceptibility to PTZ-induced seizures was observed during diazepam withdrawal after 21 and 28 days of treatment. Daily co-administration of βCCt further decreased the PTZ-seizure threshold after 21 days of treatment, whilst it prevented the diazepam withdrawal-elicited decrease of the PTZ threshold after 28 days of treatment. In conclusion, the current study suggests that the role of α1-containing GABAA receptors in mediating the development of physical dependence may vary based on the effect being studied and duration of protracted treatment. Moreover, the present data supports previous findings that the lack of activity at α1-containing GABAA receptors is not sufficient to eliminate physical dependence liability of ligands of the benzodiazepine type.

Indexed as

AnimalsAnxietyDiazepamGABA-A Receptor AgonistsMaleMotor ActivityProtein SubunitsRatsRats, WistarReceptors, GABA-ASeizuresSubstance Withdrawal SyndromeDiazepamGABA-A Receptor AgonistsGabra1 protein, ratProtein SubunitsReceptors, GABA-ABenzodiazepinesElevated plus mazePentylenetetrazole testPhysical dependence

Identifiers

PMID24695241
PMCPMC4066304
OpenAlexW2037030399

What OpenQuestion holds

Textmetadata
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Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.