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Modulatory effects of Ampicillin/Sulbactam on glial glutamate transporters and metabotropic glutamate receptor 1 as well as reinstatement to cocaine-seeking behavior.
Behav Brain Res 2017; 332:288-298BB

Abstract

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 (20mg/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) (200mg/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.

Authors+Show Affiliations

Department of Pharmacology and Experimental Therapeutics, College of Pharmacy and Pharmaceutical Sciences, University of Toledo, Toledo, OH, USA.Department of Pharmacology and Experimental Therapeutics, College of Pharmacy and Pharmaceutical Sciences, University of Toledo, Toledo, OH, USA.Department of Pharmacology and Experimental Therapeutics, College of Pharmacy and Pharmaceutical Sciences, University of Toledo, Toledo, OH, USA.Department of Pharmacology and Experimental Therapeutics, College of Pharmacy and Pharmaceutical Sciences, University of Toledo, Toledo, OH, USA. Electronic address: youssef.sari@utoledo.edu.

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

28624317

Citation

Hammad, Alaa M., et al. "Modulatory Effects of Ampicillin/Sulbactam On Glial Glutamate Transporters and Metabotropic Glutamate Receptor 1 as Well as Reinstatement to Cocaine-seeking Behavior." Behavioural Brain Research, vol. 332, 2017, pp. 288-298.
Hammad AM, Alasmari F, Althobaiti YS, et al. Modulatory effects of Ampicillin/Sulbactam on glial glutamate transporters and metabotropic glutamate receptor 1 as well as reinstatement to cocaine-seeking behavior. Behav Brain Res. 2017;332:288-298.
Hammad, A. M., Alasmari, F., Althobaiti, Y. S., & Sari, Y. (2017). Modulatory effects of Ampicillin/Sulbactam on glial glutamate transporters and metabotropic glutamate receptor 1 as well as reinstatement to cocaine-seeking behavior. Behavioural Brain Research, 332, pp. 288-298. doi:10.1016/j.bbr.2017.06.017.
Hammad AM, et al. Modulatory Effects of Ampicillin/Sulbactam On Glial Glutamate Transporters and Metabotropic Glutamate Receptor 1 as Well as Reinstatement to Cocaine-seeking Behavior. Behav Brain Res. 2017 08 14;332:288-298. PubMed PMID: 28624317.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Modulatory effects of Ampicillin/Sulbactam on glial glutamate transporters and metabotropic glutamate receptor 1 as well as reinstatement to cocaine-seeking behavior. AU - Hammad,Alaa M, AU - Alasmari,Fawaz, AU - Althobaiti,Yusuf S, AU - Sari,Youssef, Y1 - 2017/06/15/ PY - 2017/04/04/received PY - 2017/06/11/revised PY - 2017/06/13/accepted PY - 2017/6/19/pubmed PY - 2017/12/13/medline PY - 2017/6/19/entrez KW - CPP KW - Cocaine KW - GLT-1 KW - Locomotor activity KW - mGluR1 KW - xCT SP - 288 EP - 298 JF - Behavioural brain research JO - Behav. Brain Res. VL - 332 N2 - 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 (20mg/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) (200mg/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. SN - 1872-7549 UR - https://www.unboundmedicine.com/medline/citation/28624317/Modulatory_effects_of_Ampicillin/Sulbactam_on_glial_glutamate_transporters_and_metabotropic_glutamate_receptor_1_as_well_as_reinstatement_to_cocaine_seeking_behavior_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0166-4328(17)30596-X DB - PRIME DP - Unbound Medicine ER -