Citation

Alasmari MS, Almohammed OA, Hammad AM, Altulayhi KA, Alkadi BK, Alasmari AF, Alqahtani F, Sari Y, Alasmari F. Neuroscience 2023; ePub(ePub): ePub.

Copyright

(Copyright © 2023, International Brain Research Organization, Publisher Elsevier Publishing)

DOI

10.1016/j.neuroscience.2023.11.014

PMID

38036059

Abstract

INTRODUCTION: Preclinical researches demonstrated that beta-lactams have neuroprotective effects in conditions involving glutamate excitotoxicity, including substance use disorders (SUDs). This meta-analysis aims to analyze the existing evidences on the effects of beta-lactams as glutamate transporter 1 (GLT-1) upregulators in animal models of SUDs, identification of gaps in the literature, and setting the stage for potential translation into clinical phases.

METHODS: Meta-analysis was conducted on preclinical studies retrieved systematically from MEDLINE and ScienceDirect databases. Abused substances were identified by refereeing to the National Institute on Drug Abuse. The results were quantitatively described with a focus on the behavioral outcomes. Treatment effect sizes were described using standardized mean difference, and they were pooled using random effect model. I(2)-statistics was used to assess heterogeneity, and Funnel plot and Egger's test were used for assessment of publication bias.

RESULTS: Literature search yielded a total of 71 studies that were eligible to be included in the analysis. Through these studies, the effect of beta-lactams was evaluated in animal models of nicotine, cannabis, amphetamines, synthetic cathinone related, opioids, alcohol, and cocaine use disorders as well as steroids-related aggressive behaviors. Meta-analysis showed that treatments with beta-lactams consistently reduced the pooled undesired effects of the abused substances in several paradigms, including drug-self administration, conditioned place preference, seeking behaviors, hyperlocomotion, withdrawal syndromes, tolerance to analgesic effects, hyperalgesia, and hyperthermia.

CONCLUSION: This meta-analysis revealed that enhancing GLT-1 through beta-lactams seemed to be a promising treatment approach in the context of substance use disorders, as indicated by results in animal models.

Language: en

Keywords

meta-analysis; Beta lactams; Condition place preference; GLT-1; Self-administration; Substance use disorders