Different effects of morphine and morphine-6beta-glucuronide on formalin-evoked spinal glutamate release in conscious and freely moving rats.
The aim of this study was to investigate comparatively the role of spinal glutamate in the antinociceptive effect of morphine and morphine-6beta-glucuronide (M6G). The glutamate concentration in the spinal microdialysates and flinching behavior were simultaneously measured in conscious and freely moving rats after the intraplanter injection of formalin. The subcutaneous administration of morphine (0.3-3mg/kg) in these rats suppressed dose dependently both flinching behavior and spinal glutamate release induced by formalin. Similarly, the subcutaneous administration of M6G at doses of 0.1-3mg/kg suppressed the formalin-induced flinching behavior in the dose-dependent manner, but it did not cause a dose-related inhibition of spinal glutamate release. The inhibitory effects of morphine on the formalin-induced flinching behavior and spinal glutamate release were markedly attenuated by repeated treatment with this drug for 5 days in rats. Thus, there was a significant (P<0.05) correlation between antinociception and inhibitory effect on glutamate release of morphine in rats. These results suggest a significant difference between morphine and M6G in the participation of spinal glutamate for the antinociceptive effect.
Okura
Takashi
T
Department of Pharmacokinetics and Pharmacodynamics and Center of Excellence (COE) Research Program in the 21st Century, School of Pharmaceutical Sciences, University of Shizuoka, 52-1 Yada, Suruga-ku, Shizuoka 422-8526, Japan.
Komiyama
Noriyuki
N
Morita
Yuki
Y
Kimura
Midori
M
Yamada
Shizuo
S
D000818:Animals; D019540:Area Under Curve; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D005557:Formaldehyde / Q000494:pharmacology*; D018698:Glutamic Acid / Q000378:metabolism*; D008297:Male; D009020:Morphine / Q000494:pharmacology*; D009022:Morphine Derivatives / Q000494:pharmacology*; D009294:Narcotics / Q000494:pharmacology*; D010147:Pain Measurement; D051381:Rats; D013116:Spinal Cord / Q000187:drug effects* / Q000378:metabolism; D013997:Time Factors; D014851:Wakefulness
D009022:Morphine Derivatives; D009294:Narcotics; D005557:Formaldehyde; D018698:Glutamic Acid; C035349:morphine-6-glucuronide; D009020:Morphine