Dopamine D(2) receptor blockade by haloperidol. (3)H-raclopride reveals much higher occupancy than EEDQ.
Two techniques are commonly used to measure antipsychotic induced dopamine D(2) occupancy in animals: competition with a reversible radioligand (3H-raclopride) or with an irreversible receptor inactivator (EEDQ). While both of these techniques have been used in the past, there is no direct and systematic comparison. In the first direct comparison of these two methods we find that the dose of haloperidol required for blocking 50% of the dopamine D(2) receptors was 0.02 mg/kg/sc (95% CI 0.018-0.022 mg/kg) as measured using 3H-raclopride method; but was significantly higher with the EEDQ method 0.14 mg/kg/s.c. (95% CI 0.048-0.224 mg/kg). The 3H-raclopride method showed significantly lesser variance (p = 0.02) despite the higher sensitivity. This seven-fold difference in the sensitivity of the two techniques to measure antipsychotic-induced D(2) occupancy explains discrepancies in the previous studies which have used these two methods and also suggest that for future studies the 3H-raclopride method is a more sensitive and, likely, a more valid reflector of true receptor occupancy.
Kapur
S
S
Schizophrenia Program, CAMH, Ontario, Toronto, Canada. skapur@camhpet.on.ca
Barsoum
S C
SC
Seeman
P
P
D000818:Animals; D018492:Dopamine Antagonists / Q000494:pharmacology*; D006220:Haloperidol / Q000494:pharmacology*; D007700:Kinetics; D008297:Male; D011804:Quinolines / Q000494:pharmacology*; D020891:Raclopride / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017448:Receptors, Dopamine D2 / Q000187:drug effects*
D018492:Dopamine Antagonists; D011804:Quinolines; D017448:Receptors, Dopamine D2; D020891:Raclopride; C000470:EEDQ; D006220:Haloperidol