MODULATION OF NOCICEPTION BY ANGIOTENSIN II TYPE 1 RECEPTORS ANTAGONIST LOSARTAN INFUSED INTO AMYGDALA OF RATS WITH A MODEL OF DEPRESSION

The effects of angiotensin II (Ang II) and losartan (antagonist of Ang II type I receptors-AT1) infused unilaterally or bilaterally into the central nucleus of the amygdala (CeA) on nociception of male Wistar rats with a model of depression (bilateral olfactory bulbectomy-OBX) were investigated. Nociception was examined by applying mechanical pressure on the paw of the rat (analgesy-meter). The OBX rats were divided into three groups: 1st group bilaterally microinjected into CeA with Ang 11 (0.5 mu g), losartan (100 mu g,) or saline; 2nd group unilaterally (left- or right-side) microinjected into CeA with Ang II (0.5 mu g), losartan (100 mu g,) or saline, and 3rd group - sham-operated rats. It was found that Ang II microinjected bilaterally and into right-side CeA decreased the pain threshold (nociceptive effect). The inhibition of AT1 receptors by losartan microinjected uni- or bilaterally into CeA of bulb ectomized rats, increased pain threshold (antinociceptive effect) compared to the respective OBX controls; the antinociceptive effect was more pronounced in the right-side. This study for the first time provides information on a lateralized nociceptive effect of Ang II and antinociceptive effect of losartan and involvement of AT1 receptors in nociception of rats with a model of depression. These findings point to the predominant involvement of the right CeA in nociceptive responses of OBX rats, suggesting an asymmetry of the Ang II-connected behaviour responses of the left or right CeA and a different distribution of AT1 receptors in the two hemispheres.