Abstract
Major depressive disorder (MDD) and nicotine dependence are highly comorbid. MDD patients may use nicotine to ameliorate depressive symptoms. The pathophysiology of the comorbidity of these two disorders is unknown. We hypothesized that a dysfunctional dopaminergic brain reward system (BRS) might be a neurobiological link between MDD and nicotine dependence and that smoking modulates the activity of the BRS by enhancing dopaminergic activity and relieving some depressive symptoms. Eighteen nicotine-dependent, nonmedicated subjects withDiagnostic and Statistical Manual of Mental Disorders(4th edition) diagnosis of MDD and 16 nicotine-dependent, control subjects participated in a double-blind, placebo-controlled, randomized parallel study. A single 30-mg oral dose ofd-amphetamine (d-amph) was used to release dopamine and probe the activity of the BRS. Thed-amph-mediated physiological and rewarding effects were assessed at baseline and post-treatment using standardized and validated questionnaires. Our results show that d-amph significantly increased blood pressure (p < 0.001). Subjective rewarding d-amph effects increased in both groups. Negative subjective effects were reported while on placebo during nonsmoking sessions. A significant correlation between depression severity (Hamilton depression scale) andd-amph rewarding effects was found in MDD smoker subjects (Addiction Research Center Inventory composite:r = 0.89, p < 0.000; profile of mood states composite: r = 0.71,p < 0.003; and visual analog scales composite:r = 0.78, p < 0.005). These data show that smoking did not modify the response tod-amph in MDD or control subjects, but decreased overall negative mood state during placebo sessions. Severity of depression was significantly correlated with increased rewarding effects ofd-amph. Thus, although the BRS may be dysfunctional in MDD subjects, chronic nicotine use does not modify response tod-amph.
Footnotes
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This project was partially funded by the Ontario Mental Health Foundation and National Institute on Drug Abuse Grant D13630-01A1. Meeting abstracts where this work has been previously presented are as follows: Cardenas L, Busto UE, Tremblay LK, and Naranjo CA (2001) Dopaminergic activity in depressed smokers in SRNT 7th Annual Meeting (Tobacco SRNT ed) p 94, Seattle, WA; Cardenas L, Tremblay LK, Busto UE, and Naranjo CA (2001) Brain reward system in depressed smokers in ASCPT Annual Meeting (Clin Pharmacol Ther ed) 69(2), p 62, Orlando, FL; and Cardenas L, Tremblay LK, Busto UE, and Naranjo CA (2000) Dopaminergic activity in depressed smokers, in Joint Meeting of VII World Conference on Clinical Pharmacology and Therapeutics IUPHAR – Division of Clinical Pharmacology and 4th Congress of the European Association for Clinical Pharmacology and Therapeutics(Br J Clin Pharmacol ed) p 266, Florence, Italy.
- Abbreviations:
- MDD
- major depressive disorder
- BRS
- brain reward system
- d-amph
- d-amphetamine
- HAM-D
- Hamilton depression scale
- DSM-IV
- Diagnostic and Statistical Manual–Version IV
- CO
- carbon monoxide
- ARCI
- Addiction Research Center Inventory
- AG
- amphetamine group
- BG
- benzedrine group
- PCAG
- pentobarbital chlorpromazine alcohol group
- LSD
- lysergic acid diethylamide
- POMS
- profile of mood states
- VAS
- visual analog scales
- Received December 7, 2001.
- Accepted May 14, 2002.
- The American Society for Pharmacology and Experimental Therapeutics
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