Neuroscience 2005 Abstract
| Presentation Number: | 1026.18 |
|---|---|
| Abstract Title: | Dose dependence of the amphetamine-induced rCBV changes in the rodent brain: a pharmacological MRI study on the D<sub>1</sub> and D<sub>2</sub> receptor function. |
| Authors: |
Xu, H.*1,2,3
; Rosen, B. R.2,3
; Jenkins, B. G.2,3
; Chen, I.2,3
1Union Hospital, Wuhan, China 2MA, 1277 Jiefang Big Road, 430022, 3USA, 1277 Jiefang Big Road, 430022, |
| Primary Theme and Topics |
Disorders of the Nervous System - Addiction and Drugs of Abuse -- Psychostimulants and development |
| Secondary Theme and Topics | Disorders of the Nervous System<br />- Addiction and Drugs of Abuse<br />-- Addiction: Neurobiology |
| Session: |
1026. Drugs of Abuse: Psychostimulants and Development Poster |
| Presentation Time: | Wednesday, November 16, 2005 2:00 PM-3:00 PM |
| Location: | Washington Convention Center - Hall A-C, Board # UU76 |
| Keywords: | amphetamine, dopamine, D1, D2 |
Amphetamine (AMPH) is known to internalize the dopamine transporter protein (DAT) and subsequently releases massive amount of dopamine (DA). However, the degree of the released DA acting on the post-synaptic D1 versus D2 receptors is not clear. Controlling the amount of DA release by challenging rats with different doses of AMPH, we were able to probe the roles of the D1 and D2 receptors by measuring the regional cerebral blood volume (rCBV) response using pharmacological MRI (phMRI).
Methods – Sprague-Dawley rats were used in this study. rCBV response to acute AMPH challenge were acquired using IRON method with conventional gradient echo sequence (TR/TE: 305ms/6ms) in a 9.4T Bruker scanner. Four groups of Sprague-Dawley rats were challenged with different AMPH doses (iv): 0.25mg/kg (n=8), 0.5mg/kg (n=6), 1.0mg/kg (n=6), and 3.0mg/kg (n=7).
Results – There was a dose-dependent rCBV response to the AMPH challenge in the brain. AMPH of 3mg/kg and 1mg/kg induced significant rCBV increases in the caudate/putamen (CPU) and nucleus accumbens (NAc). There were no significant differences in the rCBV response between the 3mg/kg and 1mg/kg of AMPH challenges. 0.5mg/kg AMPH induced smaller rCBV increase in the CPU. 0.25mg/kg of AMPH induced significant rCBV decreases in the CPU and NAc. Since the degree of rCBV changes was determined by the net balance between the excitatory D1 and inhibitory D2 receptor functions, such a rCBV sign switch induced by low versus high AMPH dose may be due to higher affinity of DA to D2 than D1 receptor. The smaller DA release by the low dose of AMPH primarily stimulates the D2 receptor. As the AMPH dose increases, the amount of DA release increases and the D1 receptor function gradually kicks in and eventually overcomes the saturated D2 inhibitory effect to produce a net excitatory outcome.
Methods – Sprague-Dawley rats were used in this study. rCBV response to acute AMPH challenge were acquired using IRON method with conventional gradient echo sequence (TR/TE: 305ms/6ms) in a 9.4T Bruker scanner. Four groups of Sprague-Dawley rats were challenged with different AMPH doses (iv): 0.25mg/kg (n=8), 0.5mg/kg (n=6), 1.0mg/kg (n=6), and 3.0mg/kg (n=7).
Results – There was a dose-dependent rCBV response to the AMPH challenge in the brain. AMPH of 3mg/kg and 1mg/kg induced significant rCBV increases in the caudate/putamen (CPU) and nucleus accumbens (NAc). There were no significant differences in the rCBV response between the 3mg/kg and 1mg/kg of AMPH challenges. 0.5mg/kg AMPH induced smaller rCBV increase in the CPU. 0.25mg/kg of AMPH induced significant rCBV decreases in the CPU and NAc. Since the degree of rCBV changes was determined by the net balance between the excitatory D1 and inhibitory D2 receptor functions, such a rCBV sign switch induced by low versus high AMPH dose may be due to higher affinity of DA to D2 than D1 receptor. The smaller DA release by the low dose of AMPH primarily stimulates the D2 receptor. As the AMPH dose increases, the amount of DA release increases and the D1 receptor function gradually kicks in and eventually overcomes the saturated D2 inhibitory effect to produce a net excitatory outcome.
Supported by NIH 1R01 DA16187-01, 5P01 DA09467-09 & P01 AT002048
Sample Citation:
[Authors]. [Abstract Title]. Program No. XXX.XX. 2005 Neuroscience Meeting Planner. Washington, DC: Society for Neuroscience, 2005. Online.
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