Kinetic properties of the accumulation of 3H-raclopride in the mouse brain in vivo.

The kinetic properties of the accumulation of 3H-raclopride, a selective dopamine (DA) D-2 receptor antagonist, in mouse striatum in vivo was examined under various experimental conditions. The accumulation in striatum was saturable in contrast to that in cerebellum, which linearily increased with the dose. The specific binding of 3H-raclopride in the striatum, defined as the difference in the accumulation in striatum and cerebellum 30 min after the injection was completely inhibited by the D-2 receptor antagonists spiperone and (+)-butaclamol [but not (-)-butaclamol] and the DA receptor agonist N-n-propylnorapomorphine. The mean Bmax value of the specific binding was 40.7 +/- 2.8 pmol/g tissue and the mean apparent KD value, based on the dose injected, was 87.8 +/- 11.5 nmol/kg i.v. (18 different experiments). Pretreatment of the mice with a single injection of reserpine 4 h or 3 days beforehand reduced the apparent KD value which in part seemed to be due to the decreased concentration of synaptic DA. Similarly, gamma-butyrolactone injected immediately before raclopride reduced the apparent KD value, whereas amfonelic acid and (-)-amphetamine increased the observed KD values. These findings indicate competition between endogenous DA and raclopride for the D-2 receptors. Both reserpine and gamma-butyrolactone increased the apparent Bmax value by about 50% which indicates a receptor pool of DA for which raclopride does not compete.