Abstract
Exposure to ethanol commonly manifests neuroinflammation. Beta (β)-lactam antibiotics attenuate ethanol drinking through upregulation of astroglial glutamate transporters, especially glutamate transporter-1 (GLT-1), in the mesocorticolimbic brain regions, including the nucleus accumbens (Acb). However, the effect of β-lactam antibiotics on neuroinflammation in animals chronically exposed to ethanol has not been fully investigated. In this study, we evaluated the effects of ampicillin/sulbactam (AMP/SUL, 100 and 200 mg/kg, i.p.) on ethanol consumption in high alcohol drinking (HAD1) rats. Additionally, we investigated the effects of AMP/SUL on GLT-1 and N-methyl-d-aspartate (NMDA) receptor subtypes (NR2A and NR2B) in the Acb core (AcbCo) and Acb shell (AcbSh). We found that AMP/SUL at both doses attenuated ethanol consumption and restored ethanol-decreased GLT-1 and NR2B expression in the AcbSh and AcbCo, respectively. Moreover, AMP/SUL (200 mg/kg, i.p.) reduced ethanol-increased high mobility group box 1 (HMGB1) and receptor for advanced glycation end-products (RAGE) expression in the AcbSh. Moreover, both doses of AMP/SUL attenuated ethanol-elevated tumor necrosis factor-alpha (TNF-α) in the AcbSh. Our results suggest that AMP/SUL attenuates ethanol drinking and modulates NMDA receptor NR2B subunits and HMGB1-associated pathways.
Highlights
The World Health Organization reported that consumption of alcoholic beverages has increased significantly in recent years and often leads to negative health consequences [1]
Our results in this study showed that ethanol-induced reduction in NR2B was observed in the Acb core (AcbCo), and AMP/SUL treatment attenuated this effect, another study revealed that 6 month exposure to free choice 15% and 30% of ethanol induced an increase in NR2B expression in the AcbCo and central nucleus of amygdala (CeA) of P rats [8]
The present study reports that chronic ethanol consumption downregulated glutamate transporter-1 (GLT-1) expression in the Acb shell (AcbSh), but not AcbCo, of HAD1 rats
Summary
The World Health Organization reported that consumption of alcoholic beverages has increased significantly in recent years and often leads to negative health consequences [1]. We hypothesized, in this study, that chronic ethanol consumption may induce alterations on NMDAR subunits, mGluR5 and inflammatory mediators in the AcbCo and AcbSh, and that ampicillin/sulbactam (AMP/SUL) treatment, a compound that has both β-lactam antibiotic and β–lactamase inhibitor pharmacological effects, would modulate these changes. It is noteworthy that AMP/SUL treatment has been shown to attenuate reinstatement to cocaine seeking behaviors, in part by upregulating astroglial glutamate transporters in the AcbCo and AcbSh [52] To evaluate this hypothesis, we first investigated the effect of AMP/SUL treatment on chronic ethanol consumption in high alcohol drinking (HAD1) rats. We measured the protein expression of GLT-1, NR2A and NR2B subunits, mGluR5, HMGB1, RAGE, and TNF-α in the AcbCo and AcbSh. Our results showed that chronic ethanol consumption induces inflammatory response in the AcbSh, and that AMP/SUL treatment attenuates these effects. AMP/SUL might attenuate the resulting deleterious effects, including neuroinflammation
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
