Imidazoline I-2-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. I t is now known that this drug has a higher affinity for I-2-imidazoline rec eptors than alpha(2)-receptors. The roles of I-2-receptors in modulating tr ansmission in spinal reflex pathways have been investigated using the selec tive ligands RX 821029 and RS-45041-190, and, as I-2-receptors are closely associated with monoamine oxidase (MAO), the MAO inhibitors pargyline and c lorgyline. 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 motoneuron es to electrical stimulation of the sural nerve, and significantly increase d mean arterial blood pressure by approximately 10 mmHg over pre-drug value s. Neither MAO inhibitor had significant effects on reflexes, but the highe st dose of the MAO-A selective agent clorgyline (365 mu g cumulative) cause d a significant rise in blood pressure of 6 mmHg. Neither the I-2-ligands n or the MAO inhibitors prevented the further enhancement of reflexes or bloo d pressure by subsequent administration of the selective alpha(2)-adrenocep tor antagonist RX 821002. In decerebrated, spinalized rabbits, intrathecal RS-45041-190 (60 mu g, single dose) increased spinal reflex responses to 10 9% 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 ou tflows. These effects should be taken into account when interpreting the sp inal effects of imidazoline-based adrenoceptor-active drugs. (C) 2000 Elsev ier Science Ltd. All rights reserved.