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Methamphetamine‐induced behavioral sensitization in mice: alterations in mu‐opioid receptor
Author(s) -
Chiu ChiTso,
Ma Tangeng,
Ho Ing K.
Publication year - 2006
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.20.4.a676-b
Subject(s) - damgo , sensitization , methamphetamine , behavioral sensitization , μ opioid receptor , meth , chemistry , receptor , inverse agonist , pharmacology , agonist , naltrexone , opioid receptor , opioid , medicine , endocrinology , psychology , neuroscience , nucleus accumbens , monomer , organic chemistry , acrylate , polymer
We previously demonstrated that opioid receptors were involved in the induction and expression of behavioral sensitization induced by repeated injection with 2.5 mg/kg of methamphetamine (METH) once daily for 7 days. Using the same treatment regimen, the present study investigated the potential alterations in μ‐opioid receptor (MOR) associated with the induction (on days 2, 5, and 8) and expression (on days 11 and 21) of behavioral sensitization. Saturation analysis of [ 3 H]‐DAMGO binding revealed that the expression of MOR was not changed on days 2 and 5, but down‐regulated on day 8 by repeated METH treatment. After cessation of drug treatment, the expression of MOR gradually and time‐dependently returned to normal level on day 11 and up‐regulated on day 21. In contrast, no changes in expression of δ‐ and κ‐opioid receptors were detectable on any given day examined. The functional alterations in MOR were investigated by determining [ 35 S]‐GTPγ S coupling. METH treatment enhanced the potency of DAMGO for [ 35 S]‐GTPγ S coupling on days 2, 5, 11, and 21. Moreover, 1 μM of naltrexone or β‐chlornaltrexamine, a full inverse agonist of MOR, significantly suppressed the basal [ 35 S]‐GTPγ S coupling on days 2, 11, and 21. These findings indicate enhanced sensitivity and elevated constitutive activity of MOR. In summary, our data clearly demonstrate alterations in MOR and provide further support for the idea that MOR is involved in and contribute to the sensitization to locomotor stimulating effect of METH (Supported by NIH Grant RR‐P20 RRl7701 to Center of Psychiatric Neuroscience at UMC, and The Human Science Grant Foundation of Japan).