Pharmacological modulation of functional connectivity: the correlation structure underlying the phMRI response to d-amphetamine modified by selective dopamine D3 receptor antagonist SB277011A.
Pharmacological MRI (phMRI) experiments utilise fMRI time series methods to map the central effect of pharmaceutical compounds. The typical univariate maps may, however, integrate the effects of several different neurotransmitter systems or underlying mechanisms. The results may thus be spatially and/or mechanistically nonspecific. Intersubject correlation analysis based on the phMRI response amplitude can more directly identify patterns of functional connectivity underlying the central effects of an acutely administered compound. In this article, we extend this approach to experiments where the effects of one compound in modulating the response to another are of interest. Specifically, we show a modulation of the correlation structure of a probe compound (d-amphetamine) by pretreatment with the selective dopamine D3 receptor antagonist SB277011A in the rat. The strongest modifications in the correlation patterns occurred in connection with the ventral tegmental area, the source of mesolimbic dopamine projections and a key substrate in the reward system.
Schwarz
Adam J
AJ
Department of Neuroimaging, Psychiatry Centre of Excellence in Drug Discovery, GlaxoSmithKline, Via Fleming 4, 37135 Verona, Italy. adam.j.schwarz@gsk.com
Gozzi
Alessandro
A
Reese
Torsten
T
Heidbreder
Christian A
CA
Bifone
Angelo
A
D000818:Animals; D001931:Brain Mapping; D003913:Dextroamphetamine / Q000494:pharmacology*; D004298:Dopamine / Q000378:metabolism; D007091:Image Processing, Computer-Assisted; D008024:Ligands; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008297:Male; D009570:Nitriles / Q000494:pharmacology*; D016548:Prosencephalon / Q000187:drug effects / Q000473:pathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D050637:Receptors, Dopamine D3 / Q000037:antagonists & inhibitors*; D013678:Technology, Pharmaceutical / Q000379:methods; D044005:Tetrahydroisoquinolines / Q000494:pharmacology*; D013997:Time Factors; D014018:Tissue Distribution
D008024:Ligands; D009570:Nitriles; D050637:Receptors, Dopamine D3; C409982:SB 277011; D044005:Tetrahydroisoquinolines; D003913:Dextroamphetamine; D004298:Dopamine