Neuroscience 2004 Abstract
| Presentation Number: | 688.2 |
|---|---|
| Abstract Title: | Mapping the modulation of dopaminergic circuitry in amphetamine-sensitized rats using pharmacological MRI. |
| Authors: |
Chen, I.*1
; Ren, J.2
; Satpute, S. S.1
; Kosofsky, B. E.2
; Rosen, B. R.1
; Jenkins, B. G.1
; Rajadhyaksha, A. M.1
1Dept Radiology, Mass Gen. Hosp, Charlestown, MA 2Dept Neurol., Mass Gen. Hosp, Charlestown, MA |
| Primary Theme and Topics |
Neurological and Psychiatric Conditions - Addiction and Drugs of Abuse -- Psychostimulants (amphetamine and cocaine) |
| Secondary Theme and Topics | Neurological and Psychiatric Conditions<br />- Behavioral Pharmacology<br />-- Monoamines and behavior |
| Session: |
688. Drugs of Abuse: Psychostimulant Sensitization I Poster |
| Presentation Time: | Tuesday, October 26, 2004 9:00 AM-10:00 AM |
| Location: | San Diego Convention Center - Hall A-H, Board # CCC19 |
| Keywords: | Psychostimulant, Drug abuse, sensitization, MRI |
Repeated exposure to amphetamine (AMPH sensitization) causes long-lasting neuronal adaptations even after long periods of drug withdrawal. Such long-term adaptations include augmented dopamine (DA) release in the nucleus accumbens (NAcc) and downstream molecular adaptations. We have used pharmacological MRI (phMRI) to map the neuronal adaptations in chronic AMPH-treated rats and correlated the results to microdialysis measurement of DA release and c-fos expression in the NAcc.
Methods - Sprague-Dawley rats were injected with AMPH (n=6, 5-7.5mg/kg/day, i.p.) or saline (n=5) for 5 days. After 14 days of withdrawal, animals were scanned in a 9.4T Bruker scanner with an AMPH challenge (3mg/kg, i.v.). MR images were acquired repeatedly using IRON method with conventional gradient echo sequence (TR/TE 600ms/6ms). rCBV changes were quantified in selected regions. DA release by microdialysis and c-fos expression by immunohistochemistry were assessed in the NAcc.
Results - Rats from the chronic AMPH and saline pretreated groups had similar AMPH-induced rCBV increases in the striatum. rCBV increases were enhanced in the NAcc, mPFC, and thalamus and were reduced in the sensory motor cortex (smCtx) in the AMPH pretreated group. The AMPH-induced rCBV increase in the NAcc correlated with increased NAcc dopamine release and c-fos expression compared to saline pretreated rats.
Conclusions -This study provides a neurochemical and molecular correlate of AMPH-induced rCBV changes in the NAcc of chronic AMPH-treated rats. In addition this multi-modal approach allows the examination of the long-term neuroanatomical and neurobiological adaptations in the whole brain after chronic drug exposure.
Methods - Sprague-Dawley rats were injected with AMPH (n=6, 5-7.5mg/kg/day, i.p.) or saline (n=5) for 5 days. After 14 days of withdrawal, animals were scanned in a 9.4T Bruker scanner with an AMPH challenge (3mg/kg, i.v.). MR images were acquired repeatedly using IRON method with conventional gradient echo sequence (TR/TE 600ms/6ms). rCBV changes were quantified in selected regions. DA release by microdialysis and c-fos expression by immunohistochemistry were assessed in the NAcc.
Results - Rats from the chronic AMPH and saline pretreated groups had similar AMPH-induced rCBV increases in the striatum. rCBV increases were enhanced in the NAcc, mPFC, and thalamus and were reduced in the sensory motor cortex (smCtx) in the AMPH pretreated group. The AMPH-induced rCBV increase in the NAcc correlated with increased NAcc dopamine release and c-fos expression compared to saline pretreated rats.
Conclusions -This study provides a neurochemical and molecular correlate of AMPH-induced rCBV changes in the NAcc of chronic AMPH-treated rats. In addition this multi-modal approach allows the examination of the long-term neuroanatomical and neurobiological adaptations in the whole brain after chronic drug exposure.
Supported by NIDA: KO1 DA 14057, 1R01 DA16187-01, and 5P01 DA09467-09
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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