Conantokins and variants derived from cone snail venom inhibit naloxone-induced withdrawal jumping in morphine-dependent mice

The biochemical processes underlying opiate addiction are complex, but n-methyl- d-aspartate receptor (NMDAR) dysfunction appears to be one contributing factor. NMDAR antagonists, including MK-801 and memantine, have previously been shown to assuage symptoms stemming from opiate withdrawal. The cona...

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Bibliographic Details
Published in:Neuroscience letters 2006-09, Vol.405 (1), p.137-141
Main Authors: Wei, Juanjuan, Dong, Mingxin, Xiao, Cai, Jiang, Fengchao, Castellino, Francis J., Prorok, Mary, Dai, Qiuyun
Format: Article
Language:English
Subjects:
Analgesics
Animals
Biological and medical sciences
Conantokin
Conotoxins - chemistry
Conotoxins - pharmacology
Male
Medical sciences
Mice
Mollusk Venoms - chemistry
Mollusk Venoms - pharmacology
Morphine
Morphine Dependence - physiopathology
Naloxone
Naloxone - pharmacology
Narcotic Antagonists - pharmacology
Neuropharmacology
NMDA receptor
NR2B
Peptides - chemistry
Peptides - pharmacology
Pharmacology. Drug treatments
Receptors, N-Methyl-D-Aspartate - antagonists & inhibitors
Structure-Activity Relationship
Substance Withdrawal Syndrome - physiopathology
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Summary:The biochemical processes underlying opiate addiction are complex, but n-methyl- d-aspartate receptor (NMDAR) dysfunction appears to be one contributing factor. NMDAR antagonists, including MK-801 and memantine, have previously been shown to assuage symptoms stemming from opiate withdrawal. The conantokins are a small family of naturally occurring peptide toxins known to specifically antagonize the NMDAR. In the present study, the effects of wild-type and variant conantokins on the suppression of naloxone-induced jumping in morphine-dependent mice were evaluated. Our results demonstrate that NR2B-selective conantokins, viz., con-G, con-G[S 16Y] and con-G[γ 7K], are potent inhibitors of naloxone-induced jumping at low doses (2–15 nmol/kg) compared with con-T, con-R[1-17], and small-molecule antagonists of the NMDAR, including the NR2B-selective agent, ifenprodil. We conclude that the NR2B-selective conantokins may find utility as neuropharmacological tools for probing NMDAR-related mechanisms of opiate dependence.
ISSN:0304-3940
1872-7972
DOI:10.1016/j.neulet.2006.06.040