 |
|
Noradrenergic Dysregulation During Discontinuation of Cocaine Use in Addicts
Christopher J. McDougle, MD;
Jed E. Black, MD;
Robert T. Malison, MD;
Ralf C. Zimmermann, MD;
Thomas R. Kosten, MD;
George R. Heninger, MD;
Lawrence H. Price, MD
Arch Gen Psychiatry. 1994;51(9):713-719.
Abstract
| |
Background
The primary objective of the study was to prospectively determine possible noradrenergic dysregulation in cocaine addicts by assessing biochemical, behavioral, and cardiovascular responses to intravenous yohimbine hydrochloride during early and late discontinuation of cocaine use.
Methods
Twelve male and two female hospitalized cocaine-dependent subjects (mean±SD age, 30.9±7.3 years) who were not seeking primary treatment for addiction participated voluntarily for monetary remuneration. Following an initial test dose of intranasal cocaine, 2 mg/kg, cocaine addicts received single-blind, monitored cocaine insufflation, 2 mg/kg three times each day, for 3 consecutive days. One to two days (early discontinuation) and 15 to 16 days (late discontinuation) after the last dose of cocaine, subjects received double-blind, randomized intravenous infusions of yohimbine hydrochloride, 0.4 mg/kg, or placebo. Plasma 3-methoxy-4-hydroxyphenylethylene glycol (MHPG) and plasma cortisol levels, anxiety-related symptoms on clinician- and subject-rated scales, blood pressure, and heart rate were measured throughout each test day. Ten of 14 subjects completed the entire study.
Results
Subjects had a significantly greater placebocorrected MHPG response to yohimbine during early compared with late discontinuation. Subjects rated themselves significantly more nervous following yohimbine administration during early compared with late discontinuation. Seventy-one percent of subjects experienced a yohimbine-induced panic attack during early discontinuation compared with none during late discontinuation.
Conclusions
The results of this study provide evidence of an underlying dysregulation in noradrenergic function and a vulnerability to panic anxiety during early discontinuation of cocaine use in addicts. Additional investigations of noradrenergic function appear warranted to further clarify derangements associated with cocaine addiction.
Author Affiliations
From the Department of Psychiatry, the Clinical Neuroscience Research Unit of the Abraham Ribicoff Research Facilities, Connecticut Mental Health Center, Yale University School of Medicine, New Haven.
 CiteULike  Connotea  Del.icio.us  Digg  Reddit  Technorati  Twitter
What's this?
THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES
Response to Corticotropin-Releasing Hormone Infusion in Cocaine-Dependent Individuals
Brady et al.
Arch Gen Psychiatry 2009;66:422-430.
ABSTRACT
| FULL TEXT
Chronic Cocaine Self-Administration Upregulates the Norepinephrine Transporter and Alters Functional Activity in the Bed Nucleus of the Stria Terminalis of the Rhesus Monkey
Macey et al.
J. Neurosci. 2003;23:12-16.
ABSTRACT
| FULL TEXT
|
