Volume 9, Issue 4 (July & August 2018 2018)                   BCN 2018, 9(4): 289-296 | Back to browse issues page

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Mehri S, Sajjadi S S, Tabatabai S M, Hosseinzadeh H. Effects of Clavulanic Acid on the Acquisition and Reinstatement Following Morphine-induced Conditioned Place Preference in Mice. BCN. 2018; 9 (4) :289-296
URL: http://bcn.iums.ac.ir/article-1-659-en.html
1- Pharmaceutical Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran.
2- Department of Pharmacodynamics and Toxicology, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran.

Introduction: β-Lactam antibiotics like Clavulanic Acid (CA) enhances cellular glutamate uptake through activation of Glutamate Transporter subtype 1 (GLT-1) and decreases the level of glutamate in the nervous system. Based on studies, blocking the glutamate activity inhibits morphine-induced Conditioned Place Preference (CPP) in animals. Therefore, the effects of CA on the acquisition of morphine craving were evaluated using the CPP model in the current study.
Methods: CA (1, 50 and 150 mg/kg, ip) was co-administered with morphine (40 mg/kg) for 4 days in the conditioning phase. On day 8, the effects of CA on morphine preference was assessed. In another experiment, the effect of CA on reinstatement of morphine preference by a single morphine injection (10 mg/kg) was evaluated after an extinction period. 
Results: In the first method, the morphine-induced place preference was markedly reduced following administration of CA (50 and 150 mg/kg). In the second experiment, a single administration of CA (50 and 150 mg/kg) markedly inhibited the reinstatement of morphine preference on day 16. The results indicated that CA (50, 150 mg/kg) can block both morphine-induced CPP and the reinstatement of place preference following priming dose of morphine. Also memantine (as a positive control) (10 mg/kg) significantly inhibited both acquisition and reinstatement of morphine CPP.
Conclusion: Considering the important role of glutamate neurotransmission in morphine dependence, the effects of CA may be partly due to decrease in glutamate level in synaptic space and blockade of N-Methyl-D-aspartate Acid (NMDA) receptors. Although, we need further studies to determine exact cellular mechanism.

Type of Study: Original | Subject: Behavioral Neuroscience
Received: 2017/08/4 | Accepted: 2017/08/18 | Published: 2018/07/1

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