Abstract
We review the rodent, primate, and human data which have supported an endorphin-locus coeruleus (LC) disinhibition hypothesis and noradrenergic neuroanatomy for opiate withdrawal. This norepinephrine (NE) hyperactivity hypothesis can explain a large body of clinical and preclinical data and newer and more effective nonopiate treatments. Neuroanatomical, neurochemical, and neurobehavioral data which supported this norepinephrine (NE) hypothesis led to our demonstrationof potent antiwithdrawal efficancy for clonidine and lofexidine in with drawal and naturally occurring panic an danxiety states. WE tested the efficacy of clonidine and lofexidine in opiate withdrawal not only to demonstrate that these medicaitons might be new and important treatments for addicts but also to see which physilogical and affective variables would be completely reversible and thereby attributable to specific agonistic effects on presynaptic alpha-2 receptors on the LC. Near complete opiate withdrawal reversal or opiate substituti...
Published Version
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