Neuroscience 2004 Abstract
| Presentation Number: | 578.1 |
|---|---|
| Abstract Title: | Evaluating transcriptional profiles in postmortem orbitofrontal cortex from drug abuse cases using microarrays, toxicology and patient history. |
| Authors: |
Lehrmann, E.*1
; Colantuoni, C.3
; Gallegos, G.1,3
; Deep-Soboslay, A.3
; Becker, K. G.4
; Wood III, W. H.4
; Huestis, M. A.2
; Barnes, A.2
; Kleinman, J. E.3
; Weinberger, D. R.3
; Hyde, T. M.3
; Freed, W. J.1
1CNRB, NIDA IRP/NIH/DHHS, Baltimore, MD 2CDMS, NIDA IRP/NIH/DHHS, Baltimore, MD 3MD, 5500 Nathan Shock Dr, 21224, 4USA, 5500 Nathan Shock Dr, 21224, |
| Primary Theme and Topics |
Neurological and Psychiatric Conditions - Addiction and Drugs of Abuse -- Addiction: neurobiology |
| Secondary Theme and Topics | Neurological and Psychiatric Conditions<br />- Addiction and Drugs of Abuse<br />-- Neuroplasticity and addiction |
| Session: |
578. Addiction: Neurobiology III Poster |
| Presentation Time: | Monday, October 25, 2004 1:00 PM-2:00 PM |
| Location: | San Diego Convention Center - Hall A-H, Board # EEE11 |
| Keywords: | ADDICTION, COCAINE, THC, CORTEX |
The orbitofrontal cortex (OFC) is involved in intoxication, craving, bingeing and withdrawal in drug addiction (Am J Psychiatry 2002, 159:1642-1652). In the present study we examined transcriptional patterns in postmortem OFC from 34 drug abuse cases (primarily cocaine and THC) and 34 controls. For each case, duplicate NIA MGC microarrays were hybridized with 33P-labeled cDNA reverse transcribed from 8 ug total RNA.
Each drug abuse case was compared to the four best-matching controls and to a pool of all controls. Hierarchical clustering of transcriptional profiles showed that there were three main clusters, or subgroups, of drug abuse cases. For each pairing of subgroups, a subset of transcripts could be identified for which expression was increased in one subgroup and decreased in the second subgroup. The subgroups were not clearly related to drug abuse history. We are evaluating toxicological profiles by gas chromatography-mass spectrometry, and further evaluating patterns of past drug use via medical records and structured interviews with next-of-kin.
In a prior study (Pharmacogenomics J. 2003, 3, 27-40), we found that two subgroups of cocaine abuse cases showed opposite regulation of a subset of transcripts in the dorsolateral prefrontal cortex, and hypothesized that this was related to differences in chronicity and/or time since the most recent cocaine dose. The present study confirms that differential and opposite regulation of specific transcripts occurs in drug abuse, but suggests that drug abuse may involve more than two such patterns of transcriptional regulation.
Each drug abuse case was compared to the four best-matching controls and to a pool of all controls. Hierarchical clustering of transcriptional profiles showed that there were three main clusters, or subgroups, of drug abuse cases. For each pairing of subgroups, a subset of transcripts could be identified for which expression was increased in one subgroup and decreased in the second subgroup. The subgroups were not clearly related to drug abuse history. We are evaluating toxicological profiles by gas chromatography-mass spectrometry, and further evaluating patterns of past drug use via medical records and structured interviews with next-of-kin.
In a prior study (Pharmacogenomics J. 2003, 3, 27-40), we found that two subgroups of cocaine abuse cases showed opposite regulation of a subset of transcripts in the dorsolateral prefrontal cortex, and hypothesized that this was related to differences in chronicity and/or time since the most recent cocaine dose. The present study confirms that differential and opposite regulation of specific transcripts occurs in drug abuse, but suggests that drug abuse may involve more than two such patterns of transcriptional regulation.
Sample Citation:
[Authors]. [Abstract Title]. Program No. XXX.XX. 2004 Neuroscience Meeting Planner. San Diego, CA: Society for Neuroscience, 2004. Online.
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