SUMMARY1. The a2-adrenergic agonist clonidine was given by aortic injection to three groups of unanaesthetized fetal lambs in utero near term. One group was intact, the second had the brain stem transacted just above the pons, and the third had bilateral section of the carotid sinus nerves and cervical vagi.2. Clonidine had similar effects in all three groups. Electrocortical activity entered a high-voltage, low-frequency episode: breathing, neck and limb movements ceased; arterial pressure remained unchanged or increased; heart rate fell or remained unchanged, and the variation in both heart rate and blood pressure was much reduced. This state lasted 10-20 min, and was followed by a period of up to 4 h during which the cycling of electrocortical activity was rapid and irregular.3. The a2-adrenergic antagonist idazoxan (0-5-2-0 mg I.A.) blocked all the actions of clonidine. When given alone it usually induced a short period of low-voltage electrocortical activity and stimulated breathing movements. These effects were present in both the intact and brain-stem-transected groups, though the stimulation of breathing was significantly reduced by brain-stem transaction. There were no consistent effects on heart rate or blood pressure.4. The effects of clonidine on fetal heart rate and electrocortical activity were similar to those described in adults, but it also had inhibitory effects, not present in adults, on fetal breathing and somatic movements.

Environmental cues can elicit robust cocaine reward memories, contributing to relapse to cocaine abuse. Memories can be manipulated pharmacologically by interfering with reconsolidation after reactivation. Clonidine, an α2 noradrenergic receptor agonist, was tested for its ability to block reconsolidation of cocaine environmental-paired memory. Male Sprague-Dawley rats completed an 8-day cocaine place conditioning procedure to establish a cocaine place preference. Cocaine memory was reactivated by exposure to the cocaine-paired environment in a drug-free state, followed immediately by administration of clonidine (10 or 50 µg/kg) or vehicle. Cocaine place preference was retested 24 h and 1 week later. Clonidine significantly attenuated the previously established cocaine place preference when tested 1 or 7 days later. To investigate the generalizability of this effect to other drug classes, morphine conditioned place preference was tested. Clonidine administration after morphine memory reactivation did not significantly alter the expression of morphine place preference. These results suggest that clonidine can interfere with reconsolidation of cocaine memory and may be a useful approach to reduce relapse.