Expression of the NMDA receptor NR2A and NR2B subunits in the spinal cord of acute opioid tolerance rats

Abstract

Abstract: AIM: To observe the acute opioid tolerance repeated application of fentanyl in short term and examine the effects of acute Fentany l administration on protein expression of two major NMDA receptors subunits (NR2B and N R2A) in the spinal cord of rats.METHODS: 24 male Sprague-Dawley rats, weighing 200-220 g, were randomly divided into three groups with 8 rats each: Control, Saline and Fentanyl group.Fentanyl was injected subcutaneously four times at 15 min intervals (30μg/kg per injection) in Fentanyl group.Rats in Saline group received saline injections instead of Fentanyl. And noinjections were given to the rats of Control group. The paw withdraw althresh old (PWT) were measured every 30 min with a Von-Frey hair test.When the PWT of Fentanyl group returned to the baseline which had been measured before injection, an injection of morphine (5 mg/kg) was performed to every rat of these 3 groups.Subsequent changes of PWT were still measured every 30 min until the PWT of Fentanyl group re turned to the baseline again.The PWT at each time point were compared with the baseline and the corresponding one of the other two groups.Another 24 male Sprague-Dawleyrats, were randomly divided into three groups with 8 rats each: Control^*, Saline^* and Fentanyl^* group.Fentanyl was administrated as above except no morphine administrated.When the PWT of Fentanyl^* group returned to the baseline, all of the rats were killed.The spinal cord was sampled and the protein levels of NR2B and NR2A subunits were tested with the Western blotting method.RESULTS: Four fentanyl boluses (in group F) elicited an increase followed by an immediate decrease of the PWT and reduction of the analgesic effect of a subsequent morphine administration compared with the other two groups. According to the results of Western blot ting, in spinal cord, the protein level of NR2B subunit of Fentanyl^* group were higher than that of the Control^* and Saline^* group, but there was no difference of the protein level of NR2A subunit between Fentanyl^* group and the other two groups.CONCLUSION: Opioid tolerance could develop rapidly after an acute opioid exposure in rats. The protein levels of NR2B but not NR2A subunit of spinal cord are increased in acute opioid tolerance rats.

Key words: acute opioid tolerance, fentanyl, morphine, NR2A subunit of NMDA receptor, NR2B subunit of NMDA receptor

CLC Number:

R965.2

DU Jin, HUANG Yu-guang. Expression of the NMDA receptor NR2A and NR2B subunits in the spinal cord of acute opioid tolerance rats[J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2010, 15(1): 59-65.

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