Concurrent pharmacological MRI and in situ microdialysis of cocaine reveal a complex relationship between the central hemodynamic response and local dopamine concentration.
The mechanisms underlying the signal changes observed with pharmacological magnetic resonance imaging (phMRI) remain to be fully elucidated. In this study, we obtained microdialysis samples in situ at 5-min intervals during phMRI experiments using a blood pool contrast agent to correlate relative cerebral blood volume (rCBV) changes with changes in dopamine and cocaine concentrations following acute cocaine challenge (0.5 mg/kg iv) in the rat over a duration of 30 min. Three brain areas were investigated: the dorsal striatum (n = 8), the medial prefrontal cortex (mPFC; n = 5), and the primary motor cortex (n = 8). In the striatum and mPFC groups, cocaine and dopamine temporal profiles were tightly correlated, peaking during the first 5-min period postinjection, then rapidly decreasing. However, the local rCBV changes were uncorrelated and exhibited broader temporal profiles than those of cocaine and dopamine, attaining maximal response 5-10 min later. This demonstrates that direct vasoactivity of dopamine is not the dominant component of the hemodynamic response in these regions. In the motor cortex group, microdialysis revealed no local change in dopamine in any of the animals, despite large local cocaine increase and strong rCBV response, indicating that the central hemodynamic response following acute iv cocaine challenge is not driven directly by local dopamine changes in the motor cortex. The combination of phMRI and in situ microdialysis promises to be of great value in elucidating the relationship between the phMRI response to psychoactive drugs and underlying neurochemical changes.
Department of Neuroimaging, Psychiatry Centre of Excellence in Drug Discovery, GlaxoSmithKline Medicines Research Centre, 37135 Verona, Italy.
A J
AJ
Schwarz
A
A
Zocchi
T
T
Reese
A
A
Gozzi
M
M
Garzotti
G
G
Varnier
O
O
Curcuruto
I
I
Sartori
E
E
Girlanda
B
B
Biscaro
V
V
Crestan
S
S
Bertani
C
C
Heidbreder
A
A
Bifone
D000818:Animals; D001810:Blood Volume / Q000187:drug effects; D001921:Brain / Q000098:blood supply*; D003042:Cocaine / Q000493:pharmacokinetics* / Q000494:pharmacology; D003342:Corpus Striatum / Q000098:blood supply / Q000187:drug effects; D004298:Dopamine / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D006207:Half-Life; D006439:Hemodynamics / Q000187:drug effects*; D007091:Image Processing, Computer-Assisted; D007262:Infusions, Intravenous; D008279:Magnetic Resonance Imaging; D013058:Mass Spectrometry; D017551:Microdialysis; D009044:Motor Cortex / Q000098:blood supply / Q000187:drug effects; D017397:Prefrontal Cortex / Q000098:blood supply / Q000187:drug effects; D051381:Rats; D012016:Reference Values; D012039:Regional Blood Flow / Q000187:drug effects
D003042:Cocaine; D004298:Dopamine