β_lactam antibiotics against drug addiction: A novel therapeutic option

Abstract

Drug addiction as a problem for the health of the individual and the society is the result of a complex process in which there is an interaction between brain nuclei and neurotransmitters (such as glutamate). β‐lactam antibiotics, due to their enhancing properties on the glutamate transporter glutamate transporter‐1, can affect and counteract the addictive mechanisms of drugs through the regulation of extracellular glutamate. Since glutamate is a key neurotransmitter in the development of drug addiction, it seems that β‐lactams can be considered as a promising treatment for addiction. However, more research in this field is necessary to identify other mechanisms involved in their effectiveness. This article is a review of the studies conducted on the effect of β‐lactam administration in preventing the development of drug addiction, as well as their possible cellular and molecular mechanisms. This review suggests the clinical use of β‐lactam antibiotics that have weak antimicrobial properties (such as clavulanic acid) in the treatment of drug dependence.

Effects of novel beta-lactam, MC-100093, and ceftriaxone on astrocytic glutamate transporters and neuroinflammatory factors in nucleus accumbens of C57BL/6 mice exposed to escalated doses of morphine

“…Finally, MC-100093 and ceftriaxone treatments attenuated the effect of morphine-induced increase in locomotor activity. The beneficial therapeutic uses of beta-lactams for the treatments of drug dependence have been extensively studied in preclinical animal models of drugs of abuse, including alcohol, opioids, cocaine, methamphetamine and other drugs of abuse ( Abulseoud et al, 2022 , Esmaili-Shahzade-Ali-Akbari et al, 2023 ). Although, ceftriaxone has been one of the beta-lactams antibiotics studied to attenuate drug seeking behaviors involving through upregulation of GLT-1 and xCT, the novel synthetic beta-lactam, MC-100093, which doesn’t have any antibiotic action, is now considered as a potential therapeutic drug to attenuate drug-induced downregulation of GLT-1, and consequently reducing drugs of abuse seeking behaviors as demonstrated by this present study and others ( Alhaddad et al, 2022 , Knackstedt et al, 2021 , Leon et al, 2023 , Wong and Sari, 2023 ).…”