Kinetic properties of the in vivo accumulation of 3H-(-)-N-n-propylnorapomorphine in mouse brain.

(1) The influence of various dopamine (DA) receptor agonists and antagonists on the kinetic properties of the specific binding of 3H(-)-N-n-propylnorapomorphine (NPA) in the mouse striatum in vivo was studied. The specific binding of 3H-NPA, defined as the difference between the radioactivity in the striatum and cerebellum, was completely antagonized by the selective D-2 receptor antagonist raclopride but not by the selective D-1 antagonist SCH 23390, showing that the binding occurs exclusively to the D-2 receptors. (2) The selective D-2 receptor agonists pergolide and quinpirole inhibited the 3H-NPA binding biphasically at low doses, indicating that these DA receptor agonists have high affinities for a subfraction (10 to 30%) of the NPA binding sites. (3) Increasing the synaptic DA concentration by DA release [(+)-amphetamine] or uptake blockade (amfonelic acid and methylphenidate) inhibited the 3H-NPA binding in a competitive manner (unchanged Bmax, increased KD). Depletion of the DA in the synapses by gamma-butyrolactone or reserpine decreased the apparent KD value. (4) The possibility of estimating changes in the synaptic DA concentration from changes in the apparent KD is discussed. According to the results obtained, the normal concentration of DA in the synaptic cleft in mouse striatum in vivo is about 40 nmol/l and this concentration is increased 2 to 3 times by (+)-amphetamine and amfonelic acid in doses which evoke hyperactivity and stereotypic behaviour.