Imidazoline I2-receptors and spinal reflexes in the decerebrated rabbit

Idazoxan potentiates spinal reflexes in the decerebrated rabbit, an effect that has been attributed to antagonism of tonic noradrenergic inhibition. It is now known that this drug has a higher affinity for I-2-imidazoline receptors than alpha(2)-receptors. The roles of I-2-receptors in modulating transmission in spinal reflex pathways have been investigated using the selective ligands RX 821029 and RS-45041-190, and, as I-2-receptors are closely associated with monoamine oxidase (MAO), the MAO inhibitors pargyline and clorgyline. In decerebrated rabbits with an intact spinal cord, intrathecal doses of 5-365 mu g (cumulative) of the I-2-ligands augmented, to 150-180% of pre-drug levels, the reflex responses of medial gastrocnemius motoneurones to electrical stimulation of the sural nerve, and significantly increased mean arterial blood pressure by approximately 10 mmHg over pre-drug values. Neither MAO inhibitor had significant effects on reflexes, but the highest dose of the MAO-A selective agent clorgyline (365 mu g cumulative) caused a significant rise in blood pressure of 6 mmHg. Neither the I-2-ligands nor the MAO inhibitors prevented the further enhancement of reflexes or blood pressure by subsequent administration of the selective alpha(2)-adrenoceptor antagonist RX 821002. In decerebrated, spinalized rabbits, intrathecal RS-45041-190 (60 mu g, single dose) increased spinal reflex responses to 109% of pre-drug values, a significantly smaller effect than that seen in non-spinal preparations, and had no effect on brood pressure. These data show that imidazoline I-2-receptors can influence somatic and autonomic motor outflows. These effects should be taken into account when interpreting the spinal effects of imidazoline-based adrenoceptor-active drugs. (C) 2000 Elsevier Science Ltd. All rights reserved.