Imaging brain regional and cortical laminar effects of selective D3 agonists and antagonists.

Psychopharmacology
Ji-Kyung ChoiB G Jenkins

Abstract

Dopamine D3 receptors (D3R) may be important therapeutic targets for both drug abuse and dyskinesias in Parkinson's disease; however, little is known about their functional circuitry. We wished to determine if D3R antagonists SB-277011 and PG-01037 and D3R-preferring agonist 7-OH-DPAT are D3R selective in vivo. We further wished to characterize the response to D3R drugs using whole brain imaging to identify novel D3R circuitry. We investigated D3R circuitry in rats using pharmacologic MRI and challenge with selective D3R antagonists and agonist at various doses to examine regional changes in cerebral blood volume (CBV). We compared regional activation patterns with D2R/D3R agonists, as well as with prior studies of mRNA expression and autoradiography. D3R antagonists induced positive CBV changes and D3R agonist negative CBV changes in brain regions including nucleus accumbens, infralimbic cortex, thalamus, interpeduncular region, hypothalamus, and hippocampus (strongest in subiculum). All D3R-preferring drugs showed markedly greater responses in nucleus accumbens than in caudate/putamen consistent with D3R selectivity and contrary to what was observed with D2R agonists. At high doses of D3R agonist, functional changes were diff...Continue Reading

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Citations

Dec 3, 2014·Current Biology : CB·Daniel ZaldivarJozien Goense
Jul 16, 2013·Neuropharmacology·A Schrantee, L Reneman
Mar 13, 2014·Neuropharmacology·Joseph B MandevilleBruce G Jenkins
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May 19, 2021·European Journal of Radiology·Liesbeth RenemanElsmarieke van de Giessen

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