• Online Features  This Article  • References  • Full text PDF  • Reply to article  • Send to a friend  • Save in My Folder  • Save to citation manager  • Permissions  Citing Articles  • Citation map  • Citing articles on HighWire  • Citing articles on Web of Science (51)  • Contact me when this article is cited  Related Content  • Similar articles in this journal  Social Bookmarking   What's this?

I. Effects on Serotoninergic and Noradrenergic Systems in Normal Subjects

Husseini K. Manji, MD; John K. Hsiao, MD; Emile D. Risby, MD; Jerry Oliver; Matthew V. Rudorfer, MD; William Z. Potter, MD, PhD

Arch Gen Psychiatry. 1991;48(6):505-512.

Abstract

• The effects of 2 weeks of lithium carbonate administration at therapeutic plasma levels were examined in 11 normal volunteers. Serotoninergic function before and after lithium administration was assessed using low-dose intravenous clomipramine hydrochloride challenge, while urinary and plasma metabolites of norepinephrine (NE) were used to assess noradrenergic systems. Long-term lithium administration in normal subjects did not significantly or consistently enhance serotonin-mediated neuroendocrine responses but did increase measures related to neuronal release of NE. No statistically significant effects of lithium on prolactin, corticotropin, or cortisol responses to serotoninergic challenge could be detected. The probability of a type II error was assessed, and a doubling of prolactin level was unlikely to have been missed, although more modest increases (<75%) could have been overlooked. After 2 weeks of lithium administration, there were significant increases in 24-hour urinary excretion of NE, normetanephrine, and fractional NE release, compatible with increased neuronal release of NE and a lithium-induced subsensitivity in ₂-adrenergic receptor function. These changes were not statistically significant after 1 week of administration, suggesting that increased NE release is characteristic of long rather than short-term lithium administration. Since previous reports have demonstrated enhanced prolactin responses after short but not long-term lithium use, the present study points to temporal specificity in lithium's effects on both serotoninergic and noradrenergic function. Lithium's effects on NE release were consistent but small (a 16% increase), while its effects on serotoninergic responses were larger (a 50% increase in prolactin responses) but quite inconsistent, suggesting that neither of these systems is the primary site of action of lithium.

Author Affiliations

Footnotes

Reprint requests to Section on Clinical Pharmacology, Experimental Therapeutics Branch, National Institute of Mental Health, Room 2D46, Bldg 10, Bethesda, MD 20892 (Dr Hsiao).

CiteULike    Connotea    Delicious    Digg    Facebook    Reddit    Technorati    Twitter     What's this?

THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES

Standards of laboratory practice: antidepressant drug monitoring
Linder and Keck
Clin. Chem. 1998;44:1073-1084.
ABSTRACT | FULL TEXT  

Signal Transduction Pathways: Molecular Targets for Lithium's Actions
Manji et al.
Arch Gen Psychiatry 1995;52:531-543.
ABSTRACT  

Guanine Nucleotide-Binding Proteins in Bipolar Affective Disorder: Effects of Long-term Lithium Treatment
Manji et al.
Arch Gen Psychiatry 1995;52:135-144.
ABSTRACT  

Lithium Treatment Increases Norepinephrine Turnover in the Plasma of Healthy Subjects
Poirier-Littre et al.
Arch Gen Psychiatry 1993;50:72-73.
ABSTRACT  

ECT treatment does not enhance neuroendocrine responses to serotonergic challenge
Manji et al.
J Psychopharmacol 1992;6:501-508.
ABSTRACT  

The Mechanisms of Action of Lithium: II. Effects on Adenylate Cyclase Activity and {beta}-Adrenergic Receptor Binding in Normal Subjects
Risby et al.
Arch Gen Psychiatry 1991;48:513-524.
ABSTRACT