Neuroscience 2003 Abstract
| Presentation Number: | 390.17 |
|---|---|
| Abstract Title: | Dose dependent effects of the dopamine D<sub>2</sub>/D<sub>3</sub> receptor agonist quinelorane measured using pharmacological magnetic resonance imaging. |
| Authors: |
Ireland, M. D.*1
; Lowe, A. S.1
; James, M. F.
; Leslie, R. A.
; Williams, S. C. R.1
1Inst. of Psychiatry, London, United Kingdom |
| Primary Theme and Topics |
Motor Systems - Basal Ganglia -- Expression of transmitters and receptors |
| Secondary Theme and Topics | Techniques in Neuroscience<br />- Staining, tracing and imaging techniques |
| Session: |
390. Basal Ganglia: Physiology Poster |
| Presentation Time: | Monday, November 10, 2003 8:00 AM-9:00 AM |
| Location: | Morial Convention Center - Hall F-I, Board # H93 |
| Keywords: | FMRI, DOPAMINE, ACCUMBENS, STRIATUM |
Dopamine agonists considered selective for D3>D2 receptor subtypes induce hypolocomotion at low doses, and hyperlocomotion at higher doses, in rats. The causative mechanism is unclear[1]. We used functional magnetic resonance imaging to determine brain regions responding to doses of quinelorane known to induce either hypo- or hyperlocomotion. Male Sprague-Dawley rats (n=5) were anaesthetised with α-chloralose (60mg/kg i.v., 30mg/kg/hr) and scanned using multi-echo gradient-echo imaging (TE=5,10&15ms; TR=460ms; 120 volumes in 2 hours). Quinelorane (3 or 30µg/kg, s.c.) or saline vehicle were randomly administered 30-60 minutes after scan initiation. Mean echo images were realigned, normalised to a rat brain template and analysed using a general linear model[2]. 30µg/kg quinelorane, which induces hyperlocomotion, caused significant signal increases within the caudate-putamen, nucleus accumbens and olfactory nuclei (T>4.3, p<0.05), suggesting hyperlocomotor responses are mediated by areas rich in either D2 receptors (caudate-putamen), or both D2 and D3 receptors (nucleus accumbens, olfactory nuclei). 3µg/kg quinelorane, which causes hypolocomotion, produced significant signal increases in the nucleus accumbens, olfactory nuclei and islets of Calleja, but not the caudate-putamen, and signal decreases in the cerebellum, a pattern matching highest densities of D3 receptor distribution in the brain[3]. As quinelorane has high D3/D2 receptor selectivity and may be functionally selective for D3 receptors at low doses[3,4], our data suggest hypolocomotion induced by low doses of quinelorane may be mediated by D3 receptor activation.
1Horvitz et al., 2001 Psychopharmacol., 154, 350. 2Lowe et al., 2001 Proc. ISMRM. 3Levant, 1997 Pharmacol. Rev., 49, 231. 4Thorn et al., 1997 Neuropharmacol., 36, 787.
1Horvitz et al., 2001 Psychopharmacol., 154, 350. 2Lowe et al., 2001 Proc. ISMRM. 3Levant, 1997 Pharmacol. Rev., 49, 231. 4Thorn et al., 1997 Neuropharmacol., 36, 787.
Supported by GlaxoSmithKline
<B>Conflict of Interest:</B> Part-funded by GlaxoSmithKline Pharmaceuticals
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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