Tolerance to anti-nociceptive effects of sodium-salicylate and morphine decreases adenosine deaminase activity in the rat hippocampus

Adenosine has been considered as a fine-tuner of the neurotransmitters in the nerve system. Adaptive changes in the brain adenosine system occur in some patho-physiological situations such as chronic exposure to morphine. In this study, the adaptive changes in the adenosine deaminase activity as a key enzyme in the adenosine metabolism that converts adenosine to inosine and ammonia, irreversibly, due to morphine dependence and tolerance to anti-nociceptive effects of sodium-salicylate were investigated. Morphine dependence was induced by morphine administration in tap water (0.4mg/ml for 24 days). Tolerance to sodium-salicylate was induced by 6 i.p. injection (1 injection/day) of sodium-salicylate. Tolerance to antinociceptive effects of sodium-salicylate was measured by tail flick (TF) and hot plate (HP) tests. Right hippocampus was dissected, homogenized at phosphate buffer, centrifuged and then the supernatant fraction was isolated. Protein content of the samples was measured by the Bradford method. Hippocampus adenosine deaminase activity was measured by a calorimetric method of enzyme assay which is based on the direct measurement of the produced ammonia from excessive adenosine degradation by adenosine deaminase. Daily injection of Sodium-salicylate produced antinociception in early days by latency increase rather than saline injection (P<0.0001) but in the following days this antinociceptive effect progressively decreased so at the day 5 and 6 following injection it was similar to saline (P>0.05). Injection of morphine (5mg/Kg) at the day 7 showed more increase in the latency of saline injected rather than sadium-salicylate injected (P<0.001). Adenosine deaminase activity was significantly higher in sucrose administrated rather than chronic morhine administrated (P<0.05) and in saline injected rather than sodium-salicylate injected (P<0.05). Single injection of sodium-salicylate and its control shows the same activity. There was no significant difference in enzyme activity of morphine dependent with sadium-salicylate tolerance (P>0.05). This decline in the adenosine deaminase activity may be related with adaptation in brain adenosine system subsequent of dependent to morphine or tolerance to sodium-salicylate.