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


CONCLUSIONS
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.
Department of Neurosurgery, Third Affiliated Hospital of Kunming Medical University, Kunming, 650118, China.
Yaodong
Y
Fan
Haichen
H
Niu
Joshua D
JD
Rizak
Ling
L
Li
Guimei
G
Wang
Liqi
L
Xu
He
H
Ren
Hao
H
Lei
Hualin
H
Yu
D000818:Animals; D002443:Ceftriaxone / Q000008:administration & dosage*; D003213:Conditioning, Psychological / Q000187:drug effects* / Q000502:physiology; D016291:Dizocilpine Maleate / Q000008:administration & dosage*; D004359:Drug Therapy, Combination; D005108:Extinction, Psychological / Q000187:drug effects* / Q000502:physiology; D008568:Memory / Q000187:drug effects / Q000502:physiology; D009020:Morphine / Q000037:antagonists & inhibitors* / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors
D016291:Dizocilpine Maleate; D002443:Ceftriaxone; D009020:Morphine