Dopamine D(1) agonist activates temporal lobe structures in primates.
Changes in the function of dopamine D(1)-influenced neuronal pathways may be important to the pathophysiology of several human diseases. We recently developed methods for averaging functional imaging data across nonhuman primate subjects; in this study, we apply this method for the first time to map brain responses to experimental dopamine agonists in vivo. Here we report the use of positron emission tomography (PET) in seven normal baboons to measure the regional cerebral blood flow (rCBF) responses produced by an acute dose of the dopamine D(1) full agonist SKF82958. The most significant rCBF increases were in bilateral temporal lobe, including amygdala and superior temporal sulcus (6-17%, P < 0.001). Blood flow decreased in thalamus, pallidum, and pons (4-7%, P = 0.001). Furthermore the rCBF responses were dose-dependent and had a half-life of approximately 30 min, similar to that reported for the drug's antiparkinsonian effects. Absolute whole-brain blood flow did not change, suggesting that these local changes in rCBF reflect neuronal rather than direct vascular effects of the agonist. The prominent temporal lobe response to a D(1) agonist supports and extends our recent observations that levodopa produces prominent amygdala activation both in humans and in other primates. We speculate that levodopa may exert its known effects on mood in humans through increased amygdala activity, mediated in part by D(1) receptors.
Black
K J
KJ
Department of Psychiatry, Missouri 63110, USA. kevin@npg.wustl.edu
Hershey
T
T
Gado
M H
MH
Perlmutter
J S
JS
D000818:Animals; D001345:Autoradiography; D001552:Benzazepines / Q000494:pharmacology*; D002560:Cerebrovascular Circulation / Q000187:drug effects; D018491:Dopamine Agonists / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D010215:Papio; D017447:Receptors, Dopamine D1 / Q000819:agonists / Q000502:physiology*; D013702:Temporal Lobe / Q000098:blood supply / Q000737:chemistry* / Q000502:physiology*; D014055:Tomography, Emission-Computed
D001552:Benzazepines; D018491:Dopamine Agonists; D017447:Receptors, Dopamine D1; C071262:SK&F 82958