کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
5829760 | 1559002 | 2012 | 6 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
The glial cell modulators, ibudilast and its amino analog, AV1013, attenuate methamphetamine locomotor activity and its sensitization in mice
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کلمات کلیدی
موضوعات مرتبط
علوم زیستی و بیوفناوری
علم عصب شناسی
علوم اعصاب سلولی و مولکولی
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چکیده انگلیسی
Over 800,000 Americans abuse the psychomotor stimulant, methamphetamine, yet its abuse is without an approved medication. Methamphetamine induces hypermotor activity, and sensitization to this effect is suggested to represent aspects of the addiction process. Methamphetamine's regulation of 3â²-5â²-cyclic adenosine monophosphate (cAMP) levels may be partially responsible for its behavioral effects, and compounds that inhibit phosphodiesterase (PDE), the enzyme that degrades cAMP, can alter methamphetamine-induced behaviors. Methamphetamine also activates glial cells and causes a subsequent increase in pro-inflammatory cytokine levels. Modulation of glial cell activation is associated with changes in behavioral responses, and substances that oppose inflammatory activity can attenuate drug-induced behaviors. Ibudilast (aka AV411; 3-isobutyryl-2-isopropylpyrazolo-[1,5-a]pyridine), inhibits both PDE and glial pro-inflammatory activity. Ibudilast's amino analog, AV1013, modulates similar glial targets but negligibly inhibits PDE. The present study determined whether ibudilast and AV1013 would attenuate methamphetamine-induced locomotor activity and its sensitization in C57BL/6J mice. Mice were treated b.i.d. with ibudilast (1.8-13Â mg/kg), AV1013 (10-56Â mg/kg) or their vehicles intraperitoneally for 7Â days, beginning 48Â h before 5Â days of daily 1-h locomotor activity tests. Each test was initiated by either a methamphetamine (3Â mg/kg) or a saline injection. Ibudilast significantly (PÂ <Â 0.05) reduced the acute, chronic, and sensitization effects of methamphetamine's locomotor activity without significantly affecting activity by itself. AV1013 had similar anti-methamphetamine effects, suggesting that glial cell activity, by itself, can modulate methamphetamine's effects and perhaps serve as a medication target for its abuse.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: European Journal of Pharmacology - Volume 679, Issues 1â3, 15 March 2012, Pages 75-80
Journal: European Journal of Pharmacology - Volume 679, Issues 1â3, 15 March 2012, Pages 75-80
نویسندگان
Sarah E. Snider, Sarah A. Vunck, Edwin J.C.G. van den Oord, Daniel E. Adkins, Joseph L. McClay, Patrick M. Beardsley,