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Am J Psychiatry 1996; 153:83-92
Copyright © 1996 by American Psychiatric Association
Serotonergic and noradrenergic dysregulation in alcoholism: m- chlorophenylpiperazine and yohimbine effects in recently detoxified alcoholics and healthy comparison subjects
JH Krystal, E Webb, NL Cooney, HR Kranzler, SW Southwick, GR Heninger and DS Charney
Department of Psychiatry, Yale University School of Medicine, New Haven, CT.
OBJECTIVE: This study compared serotonergic (5-HT) and noradrenergic
reactivity in recently detoxified alcoholic patients and healthy comparison
subjects. METHOD: Participants were 22 male inpatients who met DSM-III-R
criteria for alcohol dependence and who were abstinent for 12-26 days and
13 male healthy comparison subjects. Subjects completed 3 days of testing
over 2 weeks under double-blind conditions that involved the intravenous
infusions of m-chlorophenylpiperazine (mCPP), yohimbine, or a saline
placebo. Drug effects on mood, physiologic responses, and plasma levels of
cortisol, prolactin, and 3- methoxy-4-hydroxyphenylglycol (MHPG) were
measured. RESULTS: Both mCPP and yohimbine infusion increased nervousness,
vital signs, and plasma cortisol, prolactin, and MHPG levels relative to
placebo Cortisol responses to mCPP were blunted in the alcoholic patients
relative to the comparison subjects. Cortisol and prolactin responses to
yohimbine were greater in the alcoholic patients, whereas their pulse
increases after yohimbine infusion were blunted. No group differences
emerged in MHPG, nervousness, or blood pressure responses to either drug.
CONCLUSIONS: This study documents persistent alterations in neuroendocrine
responsivity of both 5-HT and noradrenergic systems in alcoholic patients
after detoxification. Blunted cortisol responses to mCPP in these recently
detoxified patients may reflect reductions in 5- HT2 receptor function. The
absence of altered MHPG responses to yohimbine in the alcoholic patients
suggests that presynaptic noradrenergic responsivity is not persistently
altered in these patients. In contrast, the enhanced cortisol responses and
reduced pulse responses to yohimbine in alcoholic patients may reflect
down- regulation of postsynaptic noradrenergic receptors.
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