Agmatine inhibits morphine-induced locomotion sensitization and morphine-induced changes in striatal dopamine and metabolites in rats.
The effects of agmatine on morphine-induced locomotion sensitization and morphine-induced changes in extracellular striatal dopamine (DA) and DA metabolites were studied. The locomotor response to morphine challenge (3 mg/kg, s.c.) was enhanced in rats 3 days after repeated morphine administration, indicating development of locomotion sensitization. In vivo microdialysis demonstrated a significant increase in striatal basal levels of the DA metabolites DOPAC and HVA, but not in DA itself, and an increase in DA response to morphine challenge in rats 3 days after withdrawal. Agmatine (1, 10, 80 mg/kg) inhibited morphine-induced locomotion sensitization and the changes in DA noted above. Idazoxan attenuated the effects of agmatine on locomotion, suggesting that the effects are mediated by imidazoline receptors. In addition, repeated morphine also increased the expression of tyrosine hydroxylase mRNA in the VTA after 4 days of morphine pretreatment, while decreasing the expression of dynorphin mRNA at 3 days after withdrawal. Agmatine inhibited morphine-induced changes in dynorphin, but not in tyrosine hydroxylase mRNA expression. These data suggest that agmatine, likely by activating imidazoline receptors, inhibits morphine-induced locomotion sensitization and morphine-induced changes in extracellular DA and in dynorphin expression. Thus, agmatine deserves further study as an anti-opioid medication.
Wei
Xiao-Li
XL
Beijing Institute of Pharmacology and Toxicology, TaiPing Road 27, Beijing 100850, China.
Su
Rui-Bin
RB
Wu
Ning
N
Lu
Xin-Qiang
XQ
Zheng
Jian-Quan
JQ
Li
Jin
J
D015102:3,4-Dihydroxyphenylacetic Acid / Q000378:metabolism; D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000376:Agmatine / Q000494:pharmacology*; D000704:Analysis of Variance; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D003342:Corpus Striatum / Q000187:drug effects*; D004298:Dopamine / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D004347:Drug Interactions; D004399:Dynorphins / Q000235:genetics / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects; D006719:Homovanillic Acid / Q000378:metabolism; D019329:Idazoxan / Q000494:pharmacology; D008124:Locomotion / Q000187:drug effects*; D008297:Male; D009020:Morphine / Q000008:administration & dosage*; D009294:Narcotics / Q000008:administration & dosage*; D051381:Rats; D017208:Rats, Wistar; D013997:Time Factors
D000317:Adrenergic alpha-Antagonists; D009294:Narcotics; D015102:3,4-Dihydroxyphenylacetic Acid; D000376:Agmatine; D004399:Dynorphins; D009020:Morphine; D004298:Dopamine; D006719:Homovanillic Acid; D019329:Idazoxan