Increased dopamine D2High receptors in amphetamine-sensitized rats, measured by the agonist [3H](+)PHNO

Repeated injections of amphetamine causes animals to become sensitized and supersensitive to DA. Previous work showed that the striata from such sensitized rats revealed a 3.5-fold increase in the density of D2(High) DA receptors, as measured by the guanine-nucleotide-sensitive component of [H-3]raclopride binding. The present study was done to confirm these earlier findings by different methods and different ligands. The striata from amphetamine-sensitized rats showed an increase of 2.2-fold in the density of guanine-nueleotide-sensitive D2 receptors labeled by saturation experiments with [H-3](+)PHNO. The proportion of D2 High receptors was also found to increase 2.5-fold using the method of competition between DA and [H-3]domperidone. The overall 2.2-3.5-fold increase of DA D2(High) receptors may explain why amphetamine-sensitized animals are much more sensitive to DA agonists, even though the total density of D2 receptors may apparently be unchanged or even decreased.