The anthraquinone derivative emodin attenuates methamphetamine-induced hyperlocomotion and startle response in rats.

Abstract

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.

• Authors: Makoto Mizuno, Hiroki Kawamura, Yuta Ishizuka, Hidekazu Sotoyama, Hiroyuki Nawa
• Journal: Pharmacology, biochemistry, and behavior (Pharmacol Biochem Behav) Vol. 97 Issue 2 Pg. 392-8 (Dec 2010) ISSN: 1873-5177 [Electronic] United States
• PMID: 20863847 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2010 Elsevier Inc. All rights reserved.

Chemical References

• Biogenic Monoamines
• Central Nervous System Stimulants
• Serotonin
• Methamphetamine
• Mitogen-Activated Protein Kinase 1
• Mitogen-Activated Protein Kinase 3
• Emodin
• Dopamine

Topics

• Animals
• Biogenic Monoamines (metabolism)
• Blotting, Western
• Central Nervous System Stimulants (antagonists & inhibitors, pharmacology)
• Dopamine (metabolism)
• Dose-Response Relationship, Drug
• Electrophoresis, Polyacrylamide Gel
• Emodin (pharmacology)
• Methamphetamine (antagonists & inhibitors, pharmacology)
• Mitogen-Activated Protein Kinase 1 (antagonists & inhibitors)
• Mitogen-Activated Protein Kinase 3 (antagonists & inhibitors)
• Motor Activity (drug effects)
• Rats
• Rats, Sprague-Dawley
• Reflex, Startle (drug effects)
• Serotonin (metabolism)
• Signal Transduction (drug effects)
• Stereotyped Behavior (drug effects)