PET imaging of the serotonin transporter and 5HT1A receptor in alcohol dependence

Background—Rodent models as well as studies in humans have suggested alterations in serotonin (5HT) innervation and transmission in early onset genetically determined or type II alcoholism. This study examines two indices of serotonergic transmission, 5HT transporter levels and 5-HT1A availability, in vivo, in type II alcoholism. This is the first report of combined tracers for pre and post-synaptic serotonergic transmission in the same alcoholic subjects and the first study of 5HT1A receptors in alcoholism. Method—Fourteen alcohol dependent subjects were scanned (11 with both tracers, 1 with [11C] DASB only and two with [11C]WAY100635 only). Twelve healthy controls (HC) subjects were scanned with [11C]DASB and another 13 were scanned with [11C]WAY100635. Binding Potential (BPp, mL/cm3) and the specific to nonspecific partition coefficient (BPND, unitless) were derived for both tracers using 2 tissue compartment model and compared to HC across different brain regions. Relationships to severity of alcoholism were assessed. Results—No significant differences were observed in regional BPp or BPND between patients and controls in any of the regions examined. No significant relationships were observed between regional 5HT transporter availability, 5-HT1A availability, and disease severity with the exception of a significant negative correlation between SERT and years of dependence in amygdala and insula. Correspondence: Dr. Diana Martinez, New York State Psychiatric Institute, 1051 Riverside Drive, Box #31, New York, NY 10032, Telephone: (212) 543-6628, Fax: (212) 568-6171, email: dm437@columbia.edu. Financial Disclosures: Dr. Krystal reports the following: Consulting: AstraZeneca Pharmaceuticals, LP, Cypress Bioscience, Inc., HoustonPharma, Schering-Plough Research Institute, Shire Pharmaceuticals, and Pfizer Pharmaceuticals; Advisory Boards: BristolMyers Squibb, Eli Lilly and Co., Forest Laboratories, GlaxoSmithKline, Lohocla Research Corporation, Merz Pharmaceuticals, Takeda Industries, and Transcept Pharmaceuticals, Inc.; Exercisable Warrant Options: Tetragenex Pharmaceuticals Inc.; Research Support: Janssen Research Foundation (through the VA); Pending Patents: glutamatergic agents for psychiatric disorders (depression, OCD), antidepressant effects of oral ketamine, and oral ketamine for depression. Dr. Abi-Dargham reports the following: Consulting: Otsuka American Pharmaceuticals, Eli Lilly, Sanofi-Aventis, Intra-cellular Therapies; Advisory Boards: Otsuka American Pharmaceuticals; Speakers Bureau: Bristol-Meyers Squibb, Otsuka American Pharmaceuticals; Research Support; Bristol-Meyers Squibb, GlaxoSmithKline. Dr. Slifstein reports the following: Consulting: GlaxoSmithKline and Amgen Inc. Dr. Huang reports the following: Research Support: Pfizer, Inc., Eli Lilly and Co., GlaxoSmithKline. Dr. Frankle reports the following: Consulting: Sepracor, Inc., Transcept Pharmaceuticals (formerly Transoral), Eli Lilly, Inc.; Speaking Fees: Bristol-Meyers Squibb, Inc.; Research Support: GlaxoSmithKline, Inc., Sepracor, Inc. Dr. Hwang is now a full time employee of Amgen, Inc. Dr. Laruelle is now a full time employee of GlaxoSmithKline. The other authors report no biomedical financial interests or potential conflicts of interest. Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. NIH Public Access Author Manuscript Biol Psychiatry. Author manuscript; available in PMC 2010 January 15. Published in final edited form as: Biol Psychiatry. 2009 January 15; 65(2): 175–180. doi:10.1016/j.biopsych. 2008.08. 034. N IH PA Athor M anscript N IH PA Athor M anscript N IH PA Athor M anscript Conclusion—This study did not find alterations in measures of 5-HT1A or 5HT transporter levels in patients with type II alcoholism.