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To evaluate the dopamine hyperactivity hypothesis for opiate withdrawal, we measured serum prolactin (PRL) in 21 male methadone addicts during significant opiate withdrawal and after clonidine suppression of opiate withdrawal signs and symptoms. We also measured serum PRL in these addicts 4 weeks after they were free of clonidine and opiates. Serum PRL was significantly decreased during opiate withdrawal and after clonidine reversal of withdrawal symptoms when compared to serum PRL measured in the drug-free baseline samples. These data suggest that dopaminergic hyperactivity is present in opiate withdrawal, but may not be related to the signs and symptoms of withdrawal. A noradrenergic hyperactivity hypothesis is proposed to explain the neurobiological system that becomes activated in withdrawal, generates symptoms, and is inhibited after clonidine administration.
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