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. 2012 Oct 3;28(5):567–576. doi: 10.1007/s12264-012-1269-8

Combined action of MK-801 and ceftriaxone impairs the acquisition and reinstatement of morphine-induced conditioned place preference, and delays morphine extinction in rats

Yaodong Fan 1,3,5, Haichen Niu 2, Joshua D Rizak 3, Ling Li 4, Guimei Wang 4, Liqi Xu 4, He Ren 4, Hao Lei 2,✉, Hualin Yu 5,✉
PMCID: PMC5561921  PMID: 23054634

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

Footnotes

These authors contributed equally to this work.

Contributor Information

Hao Lei, Phone: +86-27-87198542, Phone: +86-871-5324888, FAX: +86-27-87198542, Email: leihao@wipm.ac.cn.

Hualin Yu, Phone: +86-27-87198542, Phone: +86-871-5324888, FAX: +86-27-87198542, Email: yuhl308@126.com.

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