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The effects of clavulanic acid and amoxicillin on cue-primed reinstatement of cocaine seeking.
Behav Neurosci 2019; 133(2):247-254BN

Abstract

Research using the cocaine self-administration and reinstatement animal model of relapse finds that the beta-lactam antibiotic, ceftriaxone, attenuates cocaine-primed reinstatement of cocaine seeking and upregulates two proteins that regulate glutamate release and reuptake (xCT and GLT-1, respectively) in the nucleus accumbens core (NAc). We tested three compounds with beta-lactam rings for their ability to attenuate cue-primed reinstatement and increase GLT-1 and xCT expression in the NAc and prefrontal cortex (PFC). Rats self-administered intravenous cocaine for 1 hr/day for 7 days then 6 hrs/day for 10 days. Cue-primed reinstatement tests began after 8-9 days of extinction training. Rats received oral vehicle, clavulanic acid (CA), amoxicillin (AMX), or CA + AMX (Augmentin; AUG) for 5 days prior to testing. Only AMX-treated rats demonstrated a reduction of cocaine-seeking that trended toward significance, warranting future investigation of a wider range of doses. In the NAc, GLT-1a expression was reduced in vehicle-treated rats relative to cocaine-naïve controls and was not restored by AMX or AUG. CA-treated rats reinstated more than vehicle-treated rats and exhibited GLT-1a and xCT expression intermediate between cocaine-naïve controls and vehicle-treated cocaine rats. In agreement with our previous work, cocaine did not decrease PFC GLT-1a expression. Cocaine reduced xCT expression in the PFC that was unchanged by any of the three compounds. These results indicate that AMX may be another beta-lactam that attenuates cocaine relapse. Furthermore, the upregulation of both GLT-1 and xCT in the NAc may be needed to attenuate cocaine seeking. (PsycINFO Database Record (c) 2019 APA, all rights reserved).

Authors+Show Affiliations

Department of Psychology, University of Florida.Department of Psychology, University of Florida.Department of Psychology, University of Florida.Department of Psychology, University of Florida.Department of Psychology, University of Florida.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

30714803

Citation

Bechard, Allison R., et al. "The Effects of Clavulanic Acid and Amoxicillin On Cue-primed Reinstatement of Cocaine Seeking." Behavioral Neuroscience, vol. 133, no. 2, 2019, pp. 247-254.
Bechard AR, Hamor PU, Wu L, et al. The effects of clavulanic acid and amoxicillin on cue-primed reinstatement of cocaine seeking. Behav Neurosci. 2019;133(2):247-254.
Bechard, A. R., Hamor, P. U., Wu, L., Schwendt, M., & Knackstedt, L. A. (2019). The effects of clavulanic acid and amoxicillin on cue-primed reinstatement of cocaine seeking. Behavioral Neuroscience, 133(2), pp. 247-254. doi:10.1037/bne0000297.
Bechard AR, et al. The Effects of Clavulanic Acid and Amoxicillin On Cue-primed Reinstatement of Cocaine Seeking. Behav Neurosci. 2019;133(2):247-254. PubMed PMID: 30714803.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - The effects of clavulanic acid and amoxicillin on cue-primed reinstatement of cocaine seeking. AU - Bechard,Allison R, AU - Hamor,Peter U, AU - Wu,Lizhen, AU - Schwendt,Marek, AU - Knackstedt,Lori A, Y1 - 2019/02/04/ PY - 2020/04/01/pmc-release PY - 2019/2/5/pubmed PY - 2019/7/23/medline PY - 2019/2/5/entrez SP - 247 EP - 254 JF - Behavioral neuroscience JO - Behav. Neurosci. VL - 133 IS - 2 N2 - Research using the cocaine self-administration and reinstatement animal model of relapse finds that the beta-lactam antibiotic, ceftriaxone, attenuates cocaine-primed reinstatement of cocaine seeking and upregulates two proteins that regulate glutamate release and reuptake (xCT and GLT-1, respectively) in the nucleus accumbens core (NAc). We tested three compounds with beta-lactam rings for their ability to attenuate cue-primed reinstatement and increase GLT-1 and xCT expression in the NAc and prefrontal cortex (PFC). Rats self-administered intravenous cocaine for 1 hr/day for 7 days then 6 hrs/day for 10 days. Cue-primed reinstatement tests began after 8-9 days of extinction training. Rats received oral vehicle, clavulanic acid (CA), amoxicillin (AMX), or CA + AMX (Augmentin; AUG) for 5 days prior to testing. Only AMX-treated rats demonstrated a reduction of cocaine-seeking that trended toward significance, warranting future investigation of a wider range of doses. In the NAc, GLT-1a expression was reduced in vehicle-treated rats relative to cocaine-naïve controls and was not restored by AMX or AUG. CA-treated rats reinstated more than vehicle-treated rats and exhibited GLT-1a and xCT expression intermediate between cocaine-naïve controls and vehicle-treated cocaine rats. In agreement with our previous work, cocaine did not decrease PFC GLT-1a expression. Cocaine reduced xCT expression in the PFC that was unchanged by any of the three compounds. These results indicate that AMX may be another beta-lactam that attenuates cocaine relapse. Furthermore, the upregulation of both GLT-1 and xCT in the NAc may be needed to attenuate cocaine seeking. (PsycINFO Database Record (c) 2019 APA, all rights reserved). SN - 1939-0084 UR - https://www.unboundmedicine.com/medline/citation/30714803/The_effects_of_clavulanic_acid_and_amoxicillin_on_cue_primed_reinstatement_of_cocaine_seeking_ L2 - http://content.apa.org/journals/bne/133/2/247 DB - PRIME DP - Unbound Medicine ER -