THE ROLE OF G PROTEIN EXPRESSION IN THE PARTICIPATION OF METABOTROPIC GLUTAMATE RECEPTOR 5 IN MORPHINE TOLERANCE

Objective: To investigate the role of intrathecal injection of metabotropic glutamate receptor 5(mGluR5) antisense oligodeoxynucleotide(ODN) on the occurrence of morphine tolerance and expressions of spinal G proteins in rats.Methods: Forty-eight male Sprague-Dawley rats were randomly divided into six groups: control group(S group,n = 14),antisense ODN group(ANT group,n = 6),mismatch ODN group(MIS group,n = 6),morphine tolerance group(M group,n = 8),antisense ODN plus morphine group(AM group,n = 8) and mismatch ODN plus morphine group(MM group,n = 8).Rats in ANT group,MIS group,AM group and MM group received 5 μl of intrathecal 30 nM ODN twice a day for 5 days.Rats in S and M groups were received 5 μl of 0.9% saline twice a day for 5 days.On day 6,real-time PCR was used to investigate the mRNA of mGluR5 in S group,ANT group and MIS group.From day 6,15 μg morphine was added twice a day in M group,AM group and MM group.Rats in S group received 5 μl of 0.9% saline instead of any drugs.Hot-plate test and paw pressure test were used to assess nociception and maximum percent effect(MPE) was measured.The expressions of G proteins(Gαi,Gαo,Gαq and Gβ) were detected by western blot.Results: Compared with S group,mGluR5 was reduced by 48.2% in ANT group(P 0.05).MPE% of M group and MM group decreased on day 8,with no significant difference with S group(P 0.05).MPE% of AM group on day 8 was still higher than S group(P 0.05).MPE% of AM group on day 7 and 8 was higher than M group(P 0.05).The expressions of G proteins(Gαi,Gαo,Gαq and Gβ) in M group and MM group were up-regulated,as compared with S group(P 0.05).The expressions of G proteins between AM and S groups were no significantly different(P 0.05).The expression of G protein of AM group was decreased than M group.Conclusion: Intrathecal injection of mGluR5 antisense ODN can inhibit the occurrence of morphine tolerance,and reduce the up-regulated G protein(Gαi,Gαo,Gαq and Gβ) expression in the rat spinal cord which would happen when tolerance occurs.