SPINAL NONADRENERGIC IMIDAZOLINE RECEPTORS DO NOT MEDIATE THE ANTINOCICEPTIVE ACTION OF INTRATHECAL CLONIDINE IN THE RAT

The intrathecal administration of clonidine to rats results in profoun d antinociception which is thought to be mediated through an interacti on of the agonist with spinal alpha-2 adrenergic receptors. However, c lonidine has been shown to also interact with nonadrenergic imidazolin e receptors. Consequently, this study was undertaken to determine if n onadrenergic imidazoline receptors are present in the rat spinal cord, and the extent to which they are involved in the antinociceptive acti on of spinally administered clonidine. By using the tail-flick test, t he antinociceptive action of spinally administered clonidine was found to be blocked completely by the intrathecal administration of the imi dazoline idazoxan. Similarly, yohimbine (a nonimidazoline alpha-2 adre nergic antagonist) also blocked completely the antinociceptive action of clonidine. Results of radioligand binding studies demonstrated that norepinephrine did not interact with approximately 20% of all specifi c spinal sites labeled by 4 nM [H-3]clonidine, indicating the presence of nonadrenergic spinal sites. Affinity data obtained from competitio n binding assays demonstrated that the spinal nonadrenergic sites labe led by [H-3]clonidine possess little affinity for yohimbine. Therefore , nonadrenergic imidazoline receptors are not involved in the antinoci ceptive action of spinally administered clonidine.