Research article summary (published 30 Aug 2009):

Dopaminergic response to graded dopamine concentration elicited by four amphetamine doses.

Full Abstract

We studied the metabolic responses to different DA concentrations elicited by four doses of D-amphetamine (AMPH, 0, 0.25, 0.5, 1.0, or 3.0 mg/kg). We compared the degree of DA release (via microdialysis) with striatal cAMP activity and whole brain maps of cerebral blood volume (rCBV) changes (via pharmacological MRI, phMRI). Results: AMPH increased DA release in the caudate/putamen (CPu) and cAMP activity in the CPu, nucleus accumbens (NAc), and medial prefrontal cortex (mPFC) in a linear dose-dependent manner (P < 0.0001). The cAMP data suggest that, postsynaptically, signal transduction induced by D1 receptor is stronger than that of D2 receptor at the higher doses (1-3 mg/kg). phMRI showed that, while higher doses of AMPH (3 mg/kg (n = 7) and 1 mg/kg (n = 6)) induced significant rCBV increases in the CPu and NAc, the degree of rCBV increase was much smaller with AMPH of 0.5 mg/kg (n = 6). In contrast, AMPH of 0.25 mg/kg (n = 8) induced significant rCBV decreases in the anteromedial CPu and NAc. The sign switch of rCBV in response to AMPH from low to high doses likely reflects the switching in the balance of D2/D3 stimulation vs. D1/D5 stimulation. In conclusion, degree of postsynaptic signal transduction is linearly correlated to the extracellular DA concentration. However, the presynaptic binding may dominate the overall DA innervation at the lower range of DA concentration. 2009 Wiley-Liss, Inc.

Author information

Author/s: Ren, Jiaqian (J); Xu, Haibo (H); Choi, Ji-Kyung (JK); Jenkins, Bruce G (BG); Chen, Y Iris (YI);

Affiliation: Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Charlestown, USA.

Grants: 5R01 DA16187-05 (Agency:NIDA NIH HHS) ; P01 AT002048 (Agency:NCCAM NIH HHS)

Journal and publication information

Publication Type: Journal Article; Research Support, N.I.H., Extramural

Journal: Synapse (New York, N.Y.) (Synapse), published in United States. (Language: eng)

Reference: 2009-Sep; vol 63 (issue 9) : pp 764-72

Dates: Created 2009/07/14; Completed 2009/10/09;

PMID: 19484725, status: MEDLINE (last retrieval date: 10/9/2009, IMS Date: )

Sourced from the National Library of Medicine. Abstract text and other information may be subject to copyright.

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MeSH headings (categories)

This article was linked to the MESH Headings shown below.

Amphetamine - pharmacology Animals Brain - drug effects; metabolism Brain Mapping Cerebrovascular Circulation - drug effects; physiology Cyclic AMP - metabolism Dopamine - metabolism Dopamine Uptake Inhibitors - pharmacology Dose-Response Relationship, Drug Extracellular Fluid - drug effects; metabolism Male Microdialysis

Microdialysis Neostriatum - drug effects; metabolism Nucleus Accumbens - drug effects; metabolism Prefrontal Cortex - drug effects; metabolism Rats Rats, Sprague-Dawley Receptors, Dopamine - drug effects; metabolism Receptors, Dopamine D1 - drug effects; metabolism Receptors, Dopamine D2 - drug effects; metabolism Signal Transduction - drug effects; physiology Synaptic Membranes - drug effects; metabolism Synaptic Transmission - drug effects; physiology

Associated Chemicals: Dopamine Uptake Inhibitors (0) ; Receptors, Dopamine (0) ; Receptors, Dopamine D1 (0) ; Receptors, Dopamine D2 (0) ; Amphetamine (300-62-9) ; Cyclic AMP (60-92-4)

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