Evidence map›Paper›PMID 25241066›Full record

ArticleNeuroscience2014

Serotonin in the ventral hippocampus modulates anxiety-like behavior during amphetamine withdrawal.

W Tu, A Cook, J L Scholl, M Mears, M J Watt, K J Renner, G L Forster

Abstract read
In one paragraph

Article in Neuroscience, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
26citing papers in PubMed, 2 pooled it
–field-weighted citation impact
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

26 citing papers in PubMed, 2 syntheses or guidelines pooled it.

  1. Pooled it
  2. Pooled it
  3. Targeting the 5-HTCell & bioscience · 2026
    Article
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  6. Serotonergic Input into the Cerebellar Cortex Modulates Anxiety-Like Behavior.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2025
    Article
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  19. Serotonin and brain function: a tale of two receptors.Journal of psychopharmacology (Oxford, England) · 2017
    Review
  20. Article
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

7 authors.

W TuCenter for Brain and Behavior Research, Division of Basic Biomedical Sciences, Sanford School of Medicine at the University of South Dakota, 414 East Clark Street, Vermillion, SD, USA.
A CookCenter for Brain and Behavior Research, Division of Basic Biomedical Sciences, Sanford School of Medicine at the University of South Dakota, 414 East Clark Street, Vermillion, SD, USA.
J L SchollCenter for Brain and Behavior Research, Division of Basic Biomedical Sciences, Sanford School of Medicine at the University of South Dakota, 414 East Clark Street, Vermillion, SD, USA.
M MearsCenter for Brain and Behavior Research, Division of Basic Biomedical Sciences, Sanford School of Medicine at the University of South Dakota, 414 East Clark Street, Vermillion, SD, USA.
M J WattCenter for Brain and Behavior Research, Division of Basic Biomedical Sciences, Sanford School of Medicine at the University of South Dakota, 414 East Clark Street, Vermillion, SD, USA.
K J RennerCenter for Brain and Behavior Research, Biology Department, University of South Dakota, 414 East Clark Street, Vermillion, SD, USA.
G L ForsterCenter for Brain and Behavior Research, Division of Basic Biomedical Sciences, Sanford School of Medicine at the University of South Dakota, 414 East Clark Street, Vermillion, SD, USA. Electronic address: gforster@usd.edu.

Funding

Neural Sensitivity to Stress During Drug WithdrawalR01DA019921 · NIDA · UNIVERSITY OF SOUTH DAKOTA · PI FORSTER, GINA L · 2005 to 2015
$2.4M
NIDA NIH HHS R01 DA019921
6 · The paper itself

Abstract

Withdrawal from amphetamine is associated with increased anxiety and sensitivity to stressors which are thought to contribute to relapse. Rats undergoing amphetamine withdrawal fail to exhibit stress-induced increases in serotonin (5-HT) release in the ventral hippocampus and show heightened anxiety-like behaviors. Therefore, we tested the hypothesis that reducing 5-HT levels in the ventral hippocampus is a causal mechanism in increasing anxiety-like behaviors during amphetamine withdrawal. First, we tested whether reducing 5-HT levels in the ventral hippocampus directly increases anxiety behavior. Male rats were bilaterally infused with 5,7-dihydroxytryptamine (5,7-DHT) into the ventral hippocampus, which produced a 83% decrease in ventral hippocampus 5-HT content, and were tested on the elevated plus maze (EPM) for anxiety-like behavior. Reducing ventral hippocampus 5-HT levels decreased the time spent in the open arms of the maze, suggesting that diminished ventral hippocampus 5-HT levels increases anxiety-like behavior. Next, we tested whether increasing 5-HT levels in the ventral hippocampus reverses anxiety behavior exhibited by rats undergoing amphetamine withdrawal. Rats were treated daily with either amphetamine (2.5-mg/kg, i.p.) or saline for 2weeks, and at 2weeks withdrawal, were infused with the selective serotonin reuptake inhibitor paroxetine (0.5μM) bilaterally into the ventral hippocampus and tested for anxiety-like behavior on the EPM. Rats pre-treated with amphetamine exhibited increased anxiety-like behavior on the EPM. This effect was reversed by ventral hippocampus infusion of paroxetine. Our results suggest that 5-HT levels in the ventral hippocampus are critical for regulating anxiety behavior. Increasing 5-HT levels during withdrawal may be an effective strategy for reducing anxiety-induced drug relapse.

Indexed as

5,7-DihydroxytryptamineAmphetamineAmphetamine-Related DisordersAnimalsAnxietyCentral Nervous System StimulantsDisease Models, AnimalHippocampusMaleParoxetineRatsRats, Sprague-DawleySerotoninSerotonin AgentsSubstance Withdrawal Syndrome5,7-DihydroxytryptamineAmphetamineCentral Nervous System StimulantsParoxetineSerotoninSerotonin Agentsanxietyhippocampuspsychostimulantratserotoninwithdrawal

Identifiers

PMID25241066
PMCPMC4364927

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.