The anthraquinone derivative emodin attenuates methamphetamine-induced hyperlocomotion and startle response in rats.
Abnormal signaling mediated by epidermal growth factor (EGF) or its receptor (ErbB) is implicated in the neuropathology of schizophrenia. Previously, we found that the anthraquinone derivative emodin (3-methyl-1,6,8-trihydroxyanthraquinone) inhibits ErbB1 signaling and ameliorates behavioral deficits of the schizophrenia animal model established by EGF challenge. In the present study, we assessed acute and subchronic effects of its administration on methamphetamine-triggered behavioral hyperactivation in rats. Prior subchronic administration of emodin (50mg/kg/day, 5days, p.o.) suppressed both higher acoustic startle responses and hyperlocomotion induced by acute methamphetamine challenge. In parallel, emodin also attenuated methamphetamine-induced increases in dopamine and its metabolites and decreases in serotonin and its metabolites. Emodin administered alone also had an effect on stereotypic movement but no influence on horizontal or vertical locomotor activity. In contrast to pre-treatment, post-treatment with emodin had no effect on behavioral sensitization to methamphetamine. Administration of emodin in parallel to or following repeated methamphetamine challenge failed to affect hyperlocomotion induced by methamphetamine re-challenges. These findings suggest that emodin has unique pharmacological activity, which interferes with acute methamphetamine signaling and behavior.
Mizuno
Makoto
M
Center for Transdisciplinary Research, Niigata University, Niigata, Japan. mizuno@bri.niigata-u.ac.jp
Kawamura
Hiroki
H
Ishizuka
Yuta
Y
Sotoyama
Hidekazu
H
Nawa
Hiroyuki
H
D000818:Animals; D015306:Biogenic Monoamines / Q000378:metabolism; D015153:Blotting, Western; D000697:Central Nervous System Stimulants / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D004298:Dopamine / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004591:Electrophoresis, Polyacrylamide Gel; D004642:Emodin / Q000494:pharmacology*; D008694:Methamphetamine / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D019950:Mitogen-Activated Protein Kinase 1 / Q000037:antagonists & inhibitors; D048052:Mitogen-Activated Protein Kinase 3 / Q000037:antagonists & inhibitors; D009043:Motor Activity / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013216:Reflex, Startle / Q000187:drug effects*; D012701:Serotonin / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D013239:Stereotyped Behavior / Q000187:drug effects
D015306:Biogenic Monoamines; D000697:Central Nervous System Stimulants; D012701:Serotonin; D008694:Methamphetamine; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D004642:Emodin; D004298:Dopamine