Evidence map›Paper›PMID 37765033›Full record

ArticlePharmaceuticals (Basel, Switzerland)2023

Effect of Repeated Administration of ɣ-Valerolactone (GVL) and GHB in the Mouse: Neuroadaptive Changes of the GHB and GABAergic System.

Paolo Frisoni, Giorgia Corli, Sabrine Bilel, Micaela Tirri, Laura Camilla Gasparini, Letizia Alfieri, Margherita Neri, Fabio De-Giorgio, Matteo Marti

Open access · goldAbstract read
In one paragraph

Article in Pharmaceuticals (Basel, Switzerland), 2023. 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
0.7field-weighted citation impact, top 34% 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

1 citing paper in PubMed, 3 citations in OpenAlex.

  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

9 authors at 3 institutions in 1 country.

Paolo FrisoniUnit of Legal Medicine, AUSL of Ferrara, Via Arturo Cassoli 30, 44121 Ferrara, Italy.ORCID 0000-0003-4862-2215
Giorgia CorliDepartment of Translational Medicine, Section of Legal Medicine and LTTA Centre, University of Ferrara, 44121 Ferrara, Italy.ORCID 0000-0002-2973-2446
Sabrine BilelDepartment of Translational Medicine, Section of Legal Medicine and LTTA Centre, University of Ferrara, 44121 Ferrara, Italy.
Micaela TirriDepartment of Translational Medicine, Section of Legal Medicine and LTTA Centre, University of Ferrara, 44121 Ferrara, Italy.ORCID 0000-0001-9337-9184
Laura Camilla GaspariniDepartment of Biomedical, Metabolic and Neural Sciences, Institute of Legal Medicine, University of Modena and Reggio Emilia, Via del Pozzo 71, 41124 Modena, Italy.
Letizia AlfieriDepartment of Medical Sciences, Section of Legal Medicine, University of Ferrara, Via Fossato di Mortara 70, 44121 Ferrara, Italy.ORCID 0000-0002-8234-5525
Margherita NeriDepartment of Medical Sciences, Section of Legal Medicine, University of Ferrara, Via Fossato di Mortara 70, 44121 Ferrara, Italy.ORCID 0000-0002-6459-1669
Fabio De-GiorgioDepartment of Health Care Surveillance and Bioethics, Section of Legal Medicine, Università Cattolica del Sacro Cuore, 00168 Rome, Italy.
Matteo MartiDepartment of Translational Medicine, Section of Legal Medicine and LTTA Centre, University of Ferrara, 44121 Ferrara, Italy.ORCID 0000-0001-8751-2882
University of Ferrara · ITUniversità Cattolica del Sacro Cuore · ITUniversity of Modena and Reggio Emilia · IT

Funding

Anti-Drug Policies Department, Presidency of the Council of Ministers, Italy (project: "Effects of NPS: development of a multicentre research for the information enhancement of the Early Warning System" to M. Marti and project: "Implementation of the iden Implementation of the identification and study of the effects of NPS: Development of a multicentric research to strengthen the database of the National Monitoring Centre for Drug Addiction and the Early Warning System"FIRB 2012 RBFR12LDOWUniversity of Ferrara FAR2021University of Ferrara FAR2022
6 · The paper itself

Abstract

backgroundGamma-hydroxybutyric acid (GHB) at low dosages has anxiolytic effects and promotes REM sleep and low-wave deep sleep. In the U.S., the legal form of GHB is prescribed to adults suffering from narcolepsy-associated cataplexy; the sodium salt of GHB is reserved for alcohol-addiction treatment. GHB is also a molecule of abuse and recreational use, it is a controlled substance in several countries, so gamma-valerolactone (GVL) has frequently been used as a legal substitute for it. GHB's abuse profile is most likely attributable to its anxiolytic, hypnotic, and euphoric properties, as well as its widespread availability and inexpensive/low cost on the illicit market.

methodsOur study is focused on evaluating the potential effects on the mouse brain after repeated/prolonged administration of GHB and GVL at a pharmacologically active dose (100 mg/kg) through behavioral study and immunohistochemical analysis using the markers tetraspanin 17 (TSPAN17), aldehyde dehydrogenase 5 (ALDH5A1), Gamma-aminobutyric acid type A receptor (GABA-A), and Gamma-aminobutyric acid type B receptor (GABA-B).

resultsOur findings revealed that prolonged administration of GHB and GVL at a pharmacologically active dose (100 mg/kg) can have effects on a component of the mouse brain, the intensity of which can be assessed using immunohistochemistry. The findings revealed that long-term GHB administration causes a significant plastic alteration of the GHB signaling system, with downregulation of the putative binding site (TSPAN17) and overexpression of ALDH5A1, especially in hippocampal neurons. Our findings further revealed that GABA-A and GABA-B receptors are downregulated in these brain locations, resulting in a greater decrease in GABA-B expression.

conclusionsThe goal of this study, from the point of view of forensic pathology, is to provide a new methodological strategy for better understanding the properties of this controversial substance, which could help us better grasp the unknown mechanism underlying its abuse profile.

Indexed as

cardio-respiratory changesdate-rape drugdrug facilitated sexual assaultGABAergic systemGHBGHVGVLnew psychoactive substancessedative-hypnotics

Identifiers

PMID37765033
PMCPMC10536195
OpenAlexW4386284612

What OpenQuestion 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 OpenQuestion graph.