Clonidine reverses the behavioral and respiratory effects of continuous naloxone infusion

Opiate naive rats received 24 hours of continuous subcutaneous infusion of 0.67 mg/kg/hr naloxone via osmotic minipump. As in previous studies, this induced an opiate-abstinence-like syndrome of significantly increased oxygen consumption and behavioral signs (wet-dog shakes, abdominal writhes, etc.). Clonidine, which selectively reduces central noradrenergic activity, has been shown to reverse opiate abstinence syndrome. Subcutaneous injection of 0.033 and 0.01 mg/kg clonidine totally reversed the abstinence-like behaviors and respiratory activity induced by naloxone infusion. This constitutes an additional point of similarity between opiate abstinence syndrome and the "endorphin blockade syndrome" or withdrawal from endogenous opioids resulting from chronic naloxone treatment. It is consistent with the hypothesis that hyperactivity of central noradrenergic mechanisms may contribute to both phenomena.