Relation between cortical dopamine D(2) receptor occupancy and suppression of conditioned avoidance response in non-human primate.
Suppression of the conditioned avoidance response (CAR), a useful test for screening for antipsychotic effects, has been discussed in relation to the blockade of dopaminergic transmission. The purpose of the present paper was to investigate the relationship between cortical dopamine D(2) receptor occupancy and the suppression of CAR by haloperidol in non-human primate. The avoidance rate was measured for four different doses of haloperidol treatment in a rhesus monkey, and the cortical D(2) receptor occupancy was measured in a parallel session using positron emission tomography with [(11)C]FLB 457. The successful avoidance response rate was decreased for doses of 10 and 30 microg/kg of haloperidol, and this decrement was associated with 65-77% of D(2) receptor occupancy. It is suggested that the threshold level of cortical dopamine D(2) receptor occupancy for the suppression of CAR is demonstrated in the present study.
Takano
Akihiro
A
Brain Imaging Project, National Institute of Radiological Sciences, Chiba, Japan.
Suhara
Tetsuya
T
Maeda
Jun
J
Ando
Kiyoshi
K
Okauchi
Takashi
T
Obayashi
Shigeru
S
Nakayama
Takashi
T
Kapur
Shitij
S
D000818:Animals; D001362:Avoidance Learning / Q000187:drug effects*; D002540:Cerebral Cortex / Q000000981:diagnostic imaging / Q000502:physiology*; D018492:Dopamine Antagonists / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D006220:Haloperidol / Q000494:pharmacology; D008253:Macaca mulatta; D008297:Male; D017397:Prefrontal Cortex / Q000000981:diagnostic imaging / Q000187:drug effects / Q000378:metabolism; D011759:Pyrrolidines; D019275:Radiopharmaceuticals; D017448:Receptors, Dopamine D2 / Q000187:drug effects*; D012457:Salicylamides; D013702:Temporal Lobe / Q000000981:diagnostic imaging / Q000187:drug effects / Q000378:metabolism; D014055:Tomography, Emission-Computed
D018492:Dopamine Antagonists; D011759:Pyrrolidines; D019275:Radiopharmaceuticals; D017448:Receptors, Dopamine D2; D012457:Salicylamides; C065065:FLB 457; D006220:Haloperidol