Cocaine activation discriminates dopaminergic projections by temporal response: an fMRI study in Rat.
We applied a sensitive new functional magnetic resonance imaging technique to identify the pattern and determinants of cocaine-induced brain activation in drug-naive rats. At doses greater than 0.1 mg/kg iv, cocaine produced robust activation throughout cortex with the largest magnitude increase in frontal neocortex. Additionally, we detected selective activation within dopamine-innervated subcortical regions including dorsomedial and ventrolateral striatum, nucleus accumbens region, and dorsal thalamus. Although dose response was similar among activated regions, temporal response differentiated regions along distinct anatomical boundaries with basal ganglia and limbic cortical structures, reaching maximum activation later than frontal neocortex. Pharmacological specificity was demonstrated by blocking cocaine-induced activation with SCH-23390, a selective D1 antagonist. Our data demonstrate the utility of fMRI to identify spatiotemporal patterns of cocaine-induced brain activation and implicate D1 dopaminergic mechanisms in acute cocaine action.
Marota
J J
JJ
Department of Anesthesia and Critical Care, Massachusetts General Hospital, Boston, Massachusetts, 02114, USA.
Mandeville
J B
JB
Weisskoff
R M
RM
Moskowitz
M A
MA
Rosen
B R
BR
Kosofsky
B E
BE
D000818:Animals; D001552:Benzazepines / Q000494:pharmacology; D001921:Brain / Q000187:drug effects* / Q000502:physiology*; D002560:Cerebrovascular Circulation / Q000187:drug effects; D003042:Cocaine / Q000494:pharmacology*; D004298:Dopamine / Q000502:physiology*; D018492:Dopamine Antagonists / Q000494:pharmacology; D007275:Injections, Intravenous; D008279:Magnetic Resonance Imaging; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D017447:Receptors, Dopamine D1 / Q000037:antagonists & inhibitors; D009435:Synaptic Transmission / Q000502:physiology*; D013997:Time Factors
D001552:Benzazepines; D018492:Dopamine Antagonists; D017447:Receptors, Dopamine D1; D003042:Cocaine; D004298:Dopamine