Neuroscience 2003 Abstract
| Presentation Number: | 777.8 |
|---|---|
| Abstract Title: | Mapping the response to different dopamine transporter drugs using pharmacologic MRI. |
| Authors: |
Chen, Y. I.*1
; Choi, J.1
; Mandeville, J. B.1
; Jenkins, B. G.1
1Dept. Radiol, Mass Gen. Hosp, Charlestown, MA |
| Primary Theme and Topics |
Neurological and Psychiatric Conditions - Addiction and Drugs of Abuse -- Basic mechanisms |
| Secondary Theme and Topics | Techniques in Neuroscience<br />- Staining, tracing and imaging techniques |
| Session: |
777. Addiction and Drugs of Abuse: Basic Mechanisms IV Slide |
| Presentation Time: | Wednesday, November 12, 2003 9:45 AM-9:45 AM |
| Location: | Morial Convention Center - Room 393 |
| Keywords: | dopamine transporter protein, MRI, cocaine, ritaline |
Introduction The dopamine transporter (DAT) is an important target for drugs of abuse such as cocaine as well as a therapeutic target for such conditions as narcolepsy (amphetamine) and attention deficit hyperactivity disorder (ADHD treated with ritaline or methylphenidate). Although these drugs all target the dopamine transporter, they have different behavioral effects and different affinities for the norepinephrine transprter as well as the serotonin transporter. We compared the response to four different dopamine transporter ligands to ascertain the regional differences that may exist in the activation patterns. These differences may help explain some of the relative behavioral effects.
Methods Four DAT ligands were used in phMRI studies: Cocaine(1mg/kg iv, n=32); Methylphenidate(MPH, 2mg/kg iv, n=6); CFT(0.75mg/kg iv, n=4); nomifensene(NMFS, 2mg/kg iv n=6). IRON method (1) were used to obtained relative cerebral blood volume(rCBV) changes. We quantified rCBV changes in fronto-parietal cortex (FCtx), thalamus(Thal), striatum(Str), nucleus accumbens(NAcc), cingulate(Cing) and septum.
Results The activation maps produced by these drugs have many very similar features. First, the area of largest increase in rCBV for all the ligands is FCtx, a sensory-motor area. Although all the drugs produce large striatal activation, the relative ratio of Str to FCtx is highest for CFT and NMFS. Cocaine and MPH, on the other hand, produce more activation in FCtx relative to NAcc and Str. One potential way of characterizing the abuse potential of these drugs is to measure the ratio of NAcc to Str. This ratio is low in CFT and MPH, and high in cocaine and NMFS consistent with the fact that cocaine seems to have more abuse potential than MPH. Negative rCBV changes are induced in the lateral septum, an area high in serotonin receptors, after cocaine administration.
1. Chen YC et.al., J Magn Reson Imaging, 2001. 14(5):517-24.
Methods Four DAT ligands were used in phMRI studies: Cocaine(1mg/kg iv, n=32); Methylphenidate(MPH, 2mg/kg iv, n=6); CFT(0.75mg/kg iv, n=4); nomifensene(NMFS, 2mg/kg iv n=6). IRON method (1) were used to obtained relative cerebral blood volume(rCBV) changes. We quantified rCBV changes in fronto-parietal cortex (FCtx), thalamus(Thal), striatum(Str), nucleus accumbens(NAcc), cingulate(Cing) and septum.
Results The activation maps produced by these drugs have many very similar features. First, the area of largest increase in rCBV for all the ligands is FCtx, a sensory-motor area. Although all the drugs produce large striatal activation, the relative ratio of Str to FCtx is highest for CFT and NMFS. Cocaine and MPH, on the other hand, produce more activation in FCtx relative to NAcc and Str. One potential way of characterizing the abuse potential of these drugs is to measure the ratio of NAcc to Str. This ratio is low in CFT and MPH, and high in cocaine and NMFS consistent with the fact that cocaine seems to have more abuse potential than MPH. Negative rCBV changes are induced in the lateral septum, an area high in serotonin receptors, after cocaine administration.
1. Chen YC et.al., J Magn Reson Imaging, 2001. 14(5):517-24.
Sample Citation:
[Authors]. [Abstract Title]. Program No. XXX.XX. 2003 Neuroscience Meeting Planner. New Orleans, LA: Society for Neuroscience, 2003. Online.
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