1Department of Neurosurgery, the Third Affiliated Hospital of Kunming Medical University, Kunming 650118, China
2State Key Laboratory of Magnetic Resonance and Atomic and Molecular Physics, Wuhan Institute of Physics and Mathematics, Chinese Academy of Sciences, Wuhan 430071, China
3State Key Laboratory of Brain and Cognitive Sciences, Kunming Institute of Zoology, Chinese Academy of Sciences,Kunming 650223, China
4Department of Medical Imaging, Kunming General Hospital of Chengdu Military Region, People’s Liberation Army,Kunming 650032, China
5Minimally Invasive Neurosurgery Department, the First Affiliated Hospital of Kunming Medical University, Kunming 650032, China

Abstract 

Objective It is well established that glutamate and its receptors, particularly the N-methyl-D-aspartate receptor (NMDAR), play a significant role in addiction and that the inhibition of glutamatergic hyperfunction reduces addictive behaviors in experimental animals. Specifically, NMDAR antagonists such as MK-801, and an inducer of the expression of glutamate transporter subtype-1 (GLT-1) (ceftriaxone) are known to inhibit addictive behavior. The purpose of this study was to determine whether the combined action of a low dose of MK-801 and a low dose of ceftriaxone provides better inhibition of the acquisition, extinction, and reinstatement of morphine-induced conditioned place preference (CPP)than either compound alone.Methods A morphine-paired CPP experiment was used to study the effects of low doses of MK-801, ceftriaxone and a combination of both on reward-related memory (acquisition, extinction, and reinstatement of morphine preference) in rats. Results A low dose of neither MK-801 (0.05 mg/kg, i.p.) nor ceftriaxone (25 mg/kg,i.p.) alone effectively impaired CPP behaviors. However, when applied in combination, they reduced the acquisition of morphine-induced CPP and completely prevented morphine reinstatement. Their combination also notably impaired the extinction of morphine-induced CPP. Conclusion The combined action of a low dose of an NMDAR antagonist (MK-801)and GLT-1 activation by ceftriaxone effectively changed different phases of CPP behavior.

Keywords

ceftriaxone; conditioned place preference; morphine; MK-801; glutamate transporter subtype-1

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