CEREBRAL BLOOD FLOW REGULATION IN ANESTHETIZED MORPHINE DEPENDENT RATS: THE ROLE OF THE ADENOSINE SYSTEM

Adenosine has many of the characteristics of a regulator of cerebral blood flow and adenosine receptors change in morphine dependency. In this study the changes in adenosine receptors' responsiveness of pial vessels in the hind limb area of the sensory cortex were evaluated in morphine dependent rats (MDR) using the laser Doppler flowmetry technique. Adult male Sprague Dawley rats (250-350g) were used in all experiments. Animals were made morphine dependent, thereafter local effects of adenosine receptor agonists and antagonists on regional cerebral blood flow (rCBF) were investigated. Results obtained in this study show that adenosine (10-5, 10-4, 10-3 M) increases rCBF in a dose dependent manner in sham operated, control and MDR, so that the increase of rCBF in MDR is statistically significant (p<0.01). This response was inhibited by theophylline (5× 10-5 M). Lidocaine (2%) reduced adenosine-induced increase in rCBF of MDR. N6-cyclohexyladenosine (10-6, 10-5, 10-4M) and 8- cyclopentyltheophylline (10-6M) as a selective agonist and antagonist of adenosine A1 receptors had no significant effect on rCBF in control and MDR. CGS-21680 (10-6 M) as a selective adenosine A2a receptor agonist, increased rCBF in MDR significantly (p<0.05). This response was antagonized by ZM-241385. NECA (10-6M) as a adenosine A2b receptor agonist, increased rCBF in MDR significantly (p<0.05). This response was antagonized by Alloxazine. The results of this study indicate an increase in adenosine A2 receptors' (including A2a and A2b subtypes) responsiveness in hind limb sensory cortex of MDR.