Lack of development of behavioral sensitization to methylphenidate in mice: correlation with reversible astrocytic activation.
Methamphetamine is a powerfully addictive psychostimulant that dramatically affects the mammalian central nervous system. Methylphenidate has been shown to have psychostimulus effects similar to methamphetamine. In the present study, we compared several effects of methylphenidate to those of methamphetamine. The subcutaneous administration of either methamphetamine or methylphenidate increased extracellular dopamine levels in the nucleus accumbens of mice. Interestingly, methamphetamine, but not methylphenidate, also increased the extracellular serotonin levels in this area. Further, repeated treatment with methamphetamine induced the development of sensitization to hyperlocomotion, whereas methylphenidate failed to induce behavioral sensitization. Moreover, in vitro treatment with methamphetamine, but not methylphenidate, caused long-lasting astrocytic activation in limbic neuron/glia co-cultures. These findings suggest that, unlike methamphetamine, methylphenidate shows a lack of development of behavioral sensitization to its hyperlocomotion and induces reversible astrocytic activation.
Suzuki
Tsutomu
T
Department of Toxicology, Hoshi University School of Pharmacy and Pharmaceutical Sciences, Tokyo 142-8501, Japan. suzuki@hoshi.ac.jp
Shindo
Keiko
K
Miyatake
Mayumi
M
Kurokawa
Kazuhiro
K
Higashiyama
Kimio
K
Suzuki
Masami
M
Narita
Minoru
M
D000818:Animals; D001253:Astrocytes / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D001522:Behavior, Animal / Q000187:drug effects*; D016923:Cell Death; D002478:Cells, Cultured; D000697:Central Nervous System Stimulants / Q000008:administration & dosage / Q000009:adverse effects*; D018920:Coculture Techniques; D004298:Dopamine / Q000378:metabolism; D005110:Extracellular Space / Q000378:metabolism; D007150:Immunohistochemistry; D007279:Injections, Subcutaneous; D008124:Locomotion / Q000187:drug effects; D008297:Male; D008694:Methamphetamine / Q000008:administration & dosage / Q000009:adverse effects*; D008774:Methylphenidate / Q000008:administration & dosage / Q000009:adverse effects*; D051379:Mice; D008810:Mice, Inbred C57BL; D008813:Mice, Inbred ICR; D009474:Neurons / Q000166:cytology / Q000187:drug effects; D009714:Nucleus Accumbens / Q000187:drug effects / Q000378:metabolism; D012701:Serotonin / Q000378:metabolism
D000697:Central Nervous System Stimulants; D008774:Methylphenidate; D012701:Serotonin; D008694:Methamphetamine; D004298:Dopamine