| Objective:To investigate the relationship between chronic morphine tolerance and spinal GABAB receptors in rats.Methods:Healthy male Sprague-Dawley rats weighing 200-250g were randomly divided into morphine group(Group M) and saline group(Group N) after the success of intrathecal catheterization. Chronic i.t. drug treatment consisted of twice daily i.t. injection of morphine(10μg/10μl, N=12) or saline(10μl, N=12). Following each injection, the catheter was flushed with 10μl saline. Every morning the tail-flick latency in hot water(52±0.5℃)immersion was monitored at thirty minutes before and after drug administration, which returned to baseline value as the standard of morphine tolerance. In the morning of the eleventh day, rats were killed by decapitating. Lumbar spinal cords of six rats in each group were removed to test the GABA B protein levels by western blot and the last were to investigate the GABA B mRNA levels by RT-PCR.Results:(1).At 30 minutes after administration of saline for 10 days, The TFL was basically unchanged, while the TFL of Group M increased to maximum value in the second day, then decreased until it returned to the baseline on the 10th day, tolerance to morphine analgesia occured; (2). western blot results showed that GABABi and GABAB2 protein of GABAB subtypes in Group M were significantly lower than those in Group N(P<0.05); (3).RT-PCR results showed that GABABia,GABAB1b and GABAB2 mRNA in Group M were significantly lower than those in Group N (P <0.05).Conclusion:GABAB receptor expression in spinal cord was down-regulated in chronic morphine tolerance in rats.
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