Evidence map›Paper›PMID 41492821›Full record

ArticleCNS neuroscience & therapeutics2026

Pitolisant Inhibits Alcohol Drinking and Improves Withdrawal Negative Affect Through Lateral Habenula Histaminergic Signaling in Mice.

Yan Zhao, Yixin Fu, Tianhao Liu, Zanhao Yang, Zhengzhong Yang, Bingqing Chen, Lipeng Zhou, Juntao Yang, Duo Chen, Xiaojiao Han and 4 more

Abstract read
In one paragraph

Article in CNS neuroscience & therapeutics, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
–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

1 citing paper in PubMed.

  1. Review
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

14 authors.

Yan ZhaoDepartment of Pharmacology, Naval Medical University/Second Military Medical University, Shanghai, China.
Yixin FuDepartment of Anatomy, School of Medicine, Shenzhen Campus of Sun Yat-Sen University, Sun Yat-Sen University, Shenzhen, Guangdong, China.
Tianhao LiuDepartment of Anatomy, School of Medicine, Shenzhen Campus of Sun Yat-Sen University, Sun Yat-Sen University, Shenzhen, Guangdong, China.
Zanhao YangDepartment of Anatomy, School of Medicine, Shenzhen Campus of Sun Yat-Sen University, Sun Yat-Sen University, Shenzhen, Guangdong, China.
Zhengzhong YangDepartment of Anatomy, School of Medicine, Shenzhen Campus of Sun Yat-Sen University, Sun Yat-Sen University, Shenzhen, Guangdong, China.
Bingqing ChenDepartment of Anatomy, School of Medicine, Shenzhen Campus of Sun Yat-Sen University, Sun Yat-Sen University, Shenzhen, Guangdong, China.
Lipeng ZhouDepartment of Anatomy, School of Medicine, Shenzhen Campus of Sun Yat-Sen University, Sun Yat-Sen University, Shenzhen, Guangdong, China.
Juntao YangDepartment of Anatomy, School of Medicine, Shenzhen Campus of Sun Yat-Sen University, Sun Yat-Sen University, Shenzhen, Guangdong, China.
Duo ChenDepartment of Anesthesiology, The Seventh Affiliated Hospital, Sun Yat-Sen University, Shenzhen, China.
Xiaojiao HanDepartment of Anatomy, School of Medicine, Shenzhen Campus of Sun Yat-Sen University, Sun Yat-Sen University, Shenzhen, Guangdong, China.
Ying TangClinical Skills Training Center, School of Medicine, Shenzhen Campus of Sun Yat-Sen University, Sun Yat-Sen University, Shenzhen, Guangdong, China.
Jiang-Hong YeDepartment of Anesthesiology, Pharmacology, Physiology & Neuroscience, Rutgers, The State University of New Jersey, New Jersey Medical School, Newark, New Jersey, USA.ORCID 0000-0003-2545-4239
Chao-Yu MiaoDepartment of Pharmacology, Naval Medical University/Second Military Medical University, Shanghai, China.
Rao FuDepartment of Anatomy, School of Medicine, Shenzhen Campus of Sun Yat-Sen University, Sun Yat-Sen University, Shenzhen, Guangdong, China.ORCID 0000-0002-7551-4618

Funding

Clinical Research Special Program of the Shanghai Municipal Health Commission 202140011 to Yan ZhaoFund of Shenzhen Key Laboratory ZDSYS20220606100803007National Natural Science Foundation of China 82071496 to Rao FuNational Natural Science Foundation of China 82571703 to Rao FuNatural Science Foundation of Guangdong Province 2024A1515013166 to Rao FuShenzhen Science and Technology Innovation Program JCYJ20220530145401003 to Rao FuSun Yat-sen University
6 · The paper itself

Abstract

backgroundAlcohol use disorder (AUD) is a chronic condition marked by compulsive drinking and withdrawal-related negative affect. Histamine (HA) signaling, particularly via the histamine H3 receptor (H3R), may modulate alcohol-related behaviors. We investigated the effects of pitolisant, an FDA-approved H3R antagonist, on ethanol (EtOH)-related behaviors in mice.

methodAdult male C57BL/6J mice underwent acute or chronic (2 or > 8 weeks) intermittent alcohol exposure. Pitolisant pretreatment was administered, and then pharmacological behavior, histologic, and molecular assays were conducted.

resultPitolisant administration reduced acute EtOH-induced locomotor activation, conditioned place preference, and sedative effects, and also curtailed EtOH intake. It alleviated anxiety and depression-like behavior during 24-h withdrawal (Post-EtOH). Mechanistically, the Post-EtOH condition was featured by complicated brain cFos expression mapping, including elevated cFos, [HA] and [glutamine]/[glutamate] ratio in the lateral habenula (LHb). However, systemic pitolisant treatment significantly increased [norepinephrine]/[normetanephrine] ratio, and restored the diminished phosphorylated CREB and BDNF levels in the LHb. Intra-LHb H2R antagonist cimetidine infusion partly blocked the pitolisant therapeutic effect on alcohol-related behavior.

conclusionThese findings highlight the HAergic system as a critical regulator of alcohol-related behaviors. The LHb HA signaling and norepinephrine neurotransmission might underlie pitolisant's potential novel therapeutic strategy for AUD.

Indexed as

Alcohol DrinkingHabenulaHistaminePiperidinesSubstance Withdrawal SyndromeAnimalsEthanolMaleMiceMice, Inbred C57BLSignal TransductionEthanolHistaminePiperidinespitolisantalcohol use disorderalcohol withdrawalhistamine H3 receptor (H3R)lateral habenula (LHb)negative moodpitolisant

Identifiers

PMID41492821
PMCPMC12771655

What Socratic holds

Textmetadata
LicenceCC BY
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 Socratic graph.