Modulatory effects of Ampicillin/Sulbactam on glial glutamate transporters and metabotropic glutamate receptor 1 as well as reinstatement to cocaine-seeking behavior

Abstract

The glutamatergic system has an important role in cocaine-seeking behavior. Studies have reported that chronic exposure to cocaine induces downregulation of glutamate transporter-1 (GLT-1) and cystine/glutamate exchanger (xCT) in the central reward brain regions. Ceftriaxone, a β-lactam antibiotic, restored GLT-1 expression and consequently reduced cue-induced reinstatement of cocaine-seeking behavior. In this study, we investigated the reinstatement to cocaine (20 mg/kg, i.p.) seeking behavior using a conditioned place preference (CPP) paradigm in male alcohol-preferring (P) rats. In addition, we investigated the effects of Ampicillin/Sulbactam (AMP/SUL) (200 mg/kg, i.p.), a β-lactam antibiotic, on cocaine-induced reinstatement. We also investigated the effects of AMP/SUL on the expression of glial glutamate transporters and metabotropic glutamate receptor 1 (mGluR1) in the nucleus accumbens (NAc) core and shell and the dorsomedial prefrontal cortex (dmPFC). We found that AMP/SUL treatment reduced cocaine-triggered reinstatement. This effect was associated with a decrease in locomotor activity. Moreover, GLT-1 and xCT were downregulated in the NAc core and shell, but not in the dmPFC, following cocaine-primed reinstatement. However, cocaine exposure increased the expression of mGluR1 in the NAc core, but not in the NAc shell or dmPFC. Importantly, AMP/SUL treatment normalized GLT-1 and xCT expression in the NAc core and shell; however, the drug normalized mGluR1 expression in the NAc core only. Additionally, AMP/SUL increased the expression of GLT-1 and xCT in the dmPFC as compared to the water naïve group. These findings demonstrated that glial glutamate transporters and mGluR1 in the mesocorticolimbic area could be potential therapeutic targets for the attenuation of reinstatement to cocaine-seeking behavior.

Peri-adolescent drinking of ethanol and/or nicotine modulates astroglial glutamate transporters and metabotropic glutamate receptor-1 in female alcohol-preferring rats

“…Western Blot assay was performed to determine changes in expression of GLT-1, xCT, GLAST, mGluR1, and GAPDH in the NAc, HIP, and PFC as described previously (Alasmari et al, 2016b, Hammad et al, 2017. Briefly, brain tissue samples were homogenized gently using…”

“…The primary antibodies used in this study included guinea pig anti-GLT-1 (1:5000, Millipore), rabbit anti-xCT antibody (1: 1000; Abcam), rabbit anti-GLAST antibody (1: 5000; Abcam), and rabbit anti-mGluR1 (1: 3000; Millipore Bioscience Research Reagents). These antibodies have been used in our previous studies (Hammad et al, 2017).…”

Ampicillin/Sulbactam Treatment Modulates NMDA Receptor NR2B Subunit and Attenuates Neuroinflammation and Alcohol Intake in Male High Alcohol Drinking Rats

“…It is important to note that both AMP and SUL can cross the blood brain barrier and can have a therapeutic effect against bacterial infection, which is the cause of meningitis [51]. 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.…”

Different doses of methamphetamine alter long-term potentiation, level of BDNF and neuronal apoptosis in the hippocampus of reinstated rats

“…Emerging evidence reveals that activation of hippocampal glutamate receptors is directly implicated in reinstatement of psychostimulant seeking [9,10], which glutamate receptors are interplay with changes in synaptic plasticity [11]. Hippocampal synaptic plasticity is bi-directionally modulated by psychostimulant self-administration [12].…”