Neuroscience 2004 Abstract
| Presentation Number: | 45.4 |
|---|---|
| Abstract Title: | Comparisons between maps of D2 and D3 receptor agonists and antagonists using pharmacologic MRI. |
| Authors: |
Jenkins, B. G.*1
; Choi, J.1
; Chen, Y.1
; Sarkar, S. K.2
1MGH-NMR Ctr., Mass Gen Hosp, Charlestown, MA 2PA, MGH-NMR Center Bldg 149, 02129, |
| Primary Theme and Topics |
Synaptic Transmission and Excitability - Neurotransmitters -- Catecholamines |
| Secondary Theme and Topics | Techniques in Neuroscience<br />- Staining, tracing and imaging techniques |
| Session: |
45. Catecholamines I Poster |
| Presentation Time: | Saturday, October 23, 2004 4:00 PM-5:00 PM |
| Location: | San Diego Convention Center - Hall A-H, Board # G28 |
| Keywords: | ACCUMBENS, AUTORECEPTOR, D2 [D-2], FMRI |
Introduction – Dopamine D2 and D3 receptors have functions of autoreceptors on pre-synaptic neurons to regulate dopamine release. Thus, one expects different responses to antagonists and agonists. We used MRI to show that not only are different signs for the relative cerebral blood volume (rCBV) induced by these agents, but different brain regions are activated.
Methods - We used norpropylapomorphine and quinpirole (2mg/kg i.v. for both) as D2 agonists, and eticlopride as a D2 antagonist; 7-OHDPAT (2mg/kg i.v.) as a D3 agonist and a very selective D3 antagonist – SB-277011 A (10 mg/kg i.p.; Stemp et al., J. Med. Chem. 43:1878; 2000). Significant changes in rCBV via a t-test are reported.
Results - The D3 agonist 7-OHDPAT produced the large changes in the nucleus accumbens, olfactory tubercule and thalamus (rCBV changes respectively -9.7±2.0%, -17.0± 9.5%, and –7.2±3.9%). The rCBV changes were negative. The D2 agonists quinpirole and norpropylapomorphine induced negative rCBV changes in striatum and accumbens. The D2 antagonist eticlopride (0.2-2mg/kg i.v.) induced positive rCBV activation at lower doses and negative rCBV activation at higher doses with activation strongest in cingulate and thalamus. The D3 antagonist showed positive rCBV changes in accumbens (14.4±2.6%), cingulate (29.0 ±4.7%) and thalamus (15.2 ±4.1%) and nothing in striatum (n=9); or no significant change (n=7).
Discussion - The results obtained with the D2 and D3 agonists drugs are consistent with the distributions of receptors measured by mRNA expression levels or immunohistochemistry. Thus, D2 agonists induced large striatal activation while the D3 agonist showed little activation there. The antagonists can produce positive rCBV changes consistent with blockade of the DA autoreceptor, but also showed more downstream circuitry than the agonists. MRI may prove a valuable tool for investigating dynamics in these receptor systems.
.
Methods - We used norpropylapomorphine and quinpirole (2mg/kg i.v. for both) as D2 agonists, and eticlopride as a D2 antagonist; 7-OHDPAT (2mg/kg i.v.) as a D3 agonist and a very selective D3 antagonist – SB-277011 A (10 mg/kg i.p.; Stemp et al., J. Med. Chem. 43:1878; 2000). Significant changes in rCBV via a t-test are reported.
Results - The D3 agonist 7-OHDPAT produced the large changes in the nucleus accumbens, olfactory tubercule and thalamus (rCBV changes respectively -9.7±2.0%, -17.0± 9.5%, and –7.2±3.9%). The rCBV changes were negative. The D2 agonists quinpirole and norpropylapomorphine induced negative rCBV changes in striatum and accumbens. The D2 antagonist eticlopride (0.2-2mg/kg i.v.) induced positive rCBV activation at lower doses and negative rCBV activation at higher doses with activation strongest in cingulate and thalamus. The D3 antagonist showed positive rCBV changes in accumbens (14.4±2.6%), cingulate (29.0 ±4.7%) and thalamus (15.2 ±4.1%) and nothing in striatum (n=9); or no significant change (n=7).
Discussion - The results obtained with the D2 and D3 agonists drugs are consistent with the distributions of receptors measured by mRNA expression levels or immunohistochemistry. Thus, D2 agonists induced large striatal activation while the D3 agonist showed little activation there. The antagonists can produce positive rCBV changes consistent with blockade of the DA autoreceptor, but also showed more downstream circuitry than the agonists. MRI may prove a valuable tool for investigating dynamics in these receptor systems.
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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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