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.
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.
Authors: Jodie Feil; Dianne Sheppard; Paul B Fitzgerald; Murat Yücel; Dan I Lubman; John L Bradshaw Journal: Neurosci Biobehav Rev Date: 2010-03-17 Impact factor: 8.989
Authors: B R Miller; J L Dorner; M Shou; Y Sari; S J Barton; D R Sengelaub; R T Kennedy; G V Rebec Journal: Neuroscience Date: 2008-02-15 Impact factor: 3.590