Interaction between clonidine and clomipramine on analgesia and brain transmitters in different areas of mouse brain

ABSTRACT

The antinocieptive axctive of clonidine [30 micro g/Kg] I.P., clompiramine [650 micro g/Kg] I.P. and their combination was studied by the phenylquinone writhing test in mice all through 30 minutes. The effect of these drugs on the level of brain transmitters [noradrenaline. Serotonin and dopamine] was estimated in the different areas of the brain in mice [cerebral cortex, hypothalamus and thalamuns, midbrain, medulla, pones and cerebellum]. It was found that clonidine produced a 100% protection against abdominal stretch responses and it produced a significant decrease in the norepineohrine content of the cerebral cortex, thalamus and hypothalamus, [44% and 36%] respectively, with insignificant change in the 5HT and dopamine content in all areas. Clomipramine, produced a significant mean percent protection of 49% against the writhing episodes. It produced a significant increase in the norepinephrine content in the cerebral cortex and thalamus and hypothalamus by 34% and 47% respectively. Clomipramine also produced a significant increase in the 5HT content by 60% in the cerebral cortex, 45% in thalamus and hypothalamus and 48% in the midbrain with no significant change in the dopamine level. The administration of clomipramine with clonidine decreased the 100% protection to 7% against the writhing responses. Concerning the effect of the combination of clomipramine and clonidine on brain transmitters, it was found to produce a significant increase in norepinephrine in the cerebral cortex [30%] and thalamus and hypothalamus [40%] and significant increase in 5HT by 50% and 29% in cerebral cortex, thalamus and hypothalamus and midbrain respectively. No significant change in dopamine was observed. It could be councluded that although clonidine offers a promising analgesia yet its action is decreased in patients taking tricylic antidepressants due to their interaction on the brain transmitter